New compounds, their preparation and use

ABSTRACT

The present invention relates to compounds of the general formula (I)  
                 
 
     The compounds are useful in the treatment and/or prevention of conditions mediated by nuclear receptors, in particular the Peroxisome Proliferator-Activated Receptors (PPAR).

FIELD OF INVENTION

[0001] The present invention relates to novel compounds, pharmaceuticalcompositions containing them, methods for preparing the compounds andtheir use as medicaments. More specifically, compounds of the inventioncan be utilised in the treatment of conditions mediated by nuclearreceptors, in particular the Peroxisome Proliferator-Activated Receptors(PPAR). The present compounds reduce blood glucose and triglyceridelevels and are accordingly useful for the treatment of ailments anddisorders such as diabetes and obesity.

[0002] The present invention also relates to a process for thepreparation of the above said novel compounds, their derivatives, theiranalogs, their tautomeric forms, their stereoisomers, their polymorphs,their pharmaceutically acceptable salts, pharmaceutically acceptablesolvates and pharmaceutical compositions containing them.

[0003] The compounds are useful for the treatment and/or prophylaxis ofinsulin resistance (type 2 diabetes), impaired glucose tolerance,dyslipidemia, disorders related to Syndrome X such as hypertension,obesity, insulin resistance, hyperglycaemia, atherosclerosis,hyperlipidemia, coronary artery disease and other cardiovasculardisorders. The compounds of the present invention are also useful forthe treatment of certain renal diseases including glomerulonephritis,glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis:These compounds may also be useful for improving cognitive functions indementia, treating diabetic complications, psoriasis, polycystic ovariansyndrome (PCOS) and prevention and treatment of bone loss, e.g.osteoporosis.

BACKGROUND OF THE INVENTION

[0004] Coronary artery disease (CAD) is the major cause of death in type2 diabetic and metabolic syndrome patients (i.e. patients that fallwithin the ‘deadly quartet’ category of impaired glucose tolerance,insulin resistance, hypertriglyceridaemia and/or obesity).

[0005] The hypolipidaemic fibrates and antidiabetic thiazolidinedionesseparately display moderately effective triglyceride-lowering activitiesalthough they are neither potent nor efficacious enough to be a singletherapy of choice for the dyslipidaemria often observed in type 2diabetic or metabolic syndrome patients. The thiazolidinediones alsopotently lower circulating glucose levels of type 2 diabetic animalmodels and humans. However, the fibrate class of compounds are withoutbeneficial effects on glycaemia. Studies on the molecular actions ofthese compounds indicate that thiazolidinediones and fibrates exerttheir action by activating distinct transcription factors of theperoxisome proliferator activated receptor (PPAR) family, resulting inincreased and decreased expression of specific enzymes andapolipoproteins respectively, both key-players in regulation of plasmatriglyceride content. Fibrates, on the one hand, are PPARα activators,acting primarily in the liver. Thiazolidinediones, on the other hand,are high affinity ligands for PPARγ acting primarily on adipose tissue.

[0006] Adipose tissue plays a central role in lipid homeostasis and themaintenance of energy balance in vertebrates. Adipocytes store energy inthe form of triglycerides during periods of nutritional affluence andrelease it in the form of free fatty acids at times of nutritionaldeprivation. The development of white adipose tissue is the result of acontinuous differentiation process throughout life. Much evidence pointsto the central role of PPARγ activation in initiating and regulatingthis cell differentiation. Several highly specialised proteins areinduced during adipocyte differentiation, most of them being involved inlipid storage and metabolism. The exact link from activation of PPARγ tochanges in glucose metabolism, most notably a decrease in insulinresistance in muscle, has not yet been clarified. A possible link is viafree fatty acids such that activation of PPARγ induces LipoproteinLipase (LPL), Fatty Acid Transport Protein (FATP) and Acyl-CoASynthetase (ACS) in adipose tissue but not in muscle tissue. This, inturn, reduces the concentration of free fatty acids in plasmadramatically, and due to substrate competition at the cellular level,skeletal muscle and other tissues with high metabolic rates eventuallyswitch from fatty acid oxidation to glucose oxidation with decreasedinsulin resistance as a consequence.

[0007] PPARα is involved in stimulating β-oxidation of fatty acids. Inrodents, a PPARα-mediated change in the expression of genes involved infatty acid metabolism lies at the basis of the phenomenon of peroxisomeproliferation, a pleiotropic cellular response, mainly limited to liverand kidney and which can lead to hepatocarcinogenesis in rodents. Thephenomenon of peroxisome proliferation is not seen in man. In additionto its role in peroxisome proliferation in rodents, PPARα is alsoinvolved in the control of HDL cholesterol levels in rodents and humans.This effect is, at least partially, based on a PPARα-mediatedtranscriptional regulation of the major HDL apolipoproteins, apo A-I andapo A-II. The hypotriglyceridemic action of fibrates and fatty acidsalso involves PPARα and can be summarised as follows: (I) an increasedlipolysis and clearance of remnant particles, due to changes inlipoprotein lipase and apo C-III levels, (II) a stimulation of cellularfatty acid uptake and their subsequent conversion to acyl-CoAderivatives by the induction of fatty acid binding protein and acyl-CoAsynthase, (III) an induction of fatty acid b-oxidation pathways, (IV) areduction in fatty acid and triglyceride synthesis, and finally (V) adecrease in VLDL production. Hence, both enhanced catabolism oftriglyceride-rich particles as well as reduced secretion of VLDLparticles constitutes mechanisms that contribute to the hypolipidemiceffect of fibrates.

[0008] A number of compounds have been reported to be useful in thetreatment of hyperglycemia, hyperlipidemia and hypercholesterolemia(U.S. Pat. 5,306,726, PCT Publications nos. WO91/19702, WO 95/03038, WO96/04260, WO 94/13650, WO 94/01420, WO 97/36579, WO 97/25042, WO95/17394, WO 99/08501, WO 99/19313 and WO 99/16758).

SUMMARY OF THE INVENTION

[0009] It seems more and more apparent that glucose lowering as a singleapproach does not overcome the macrovascular complications associatedwith type 2 diabetes and metabolic syndrome. Novel treatments of type 2diabetes and metabolic syndrome must therefore aim at lowering both theovert hypertriglyceridaemia associated with these syndromes as well asalleviation of hyperglycaemia.

[0010] The clinical activity of fibrates and thiazolidinedionesindicates that research for compounds displaying combined PPAR α andPPAR γ activation should lead to the discovery of efficacious glucoseand triglyceride lowering drugs that have great potential in thetreatment of type 2 diabetes and the metabolic syndrome (i.e. impairedglucose tolerance, insulin resistance, hypertriglyceridaemia and/orobesity).

DETAILED DESCRIPTION OF THE INVENTION

[0011] Accordingly, the present invention relates to compounds of thegeneral formula (Ia):

[0012] wherein ring A fused to the ring containing X and N represents a5-6 membered cyclic ring, optionally substituted with one or morehalogen, perhalomethyl, hydroxy, nitro, cyano, formyl, or C₁₋₁₂alkyl,C₄₋₁₂-alkenynyl, C₂₋₁₂-alkenyl, C₂₋₁₂-alkynyl, C₁₋₁₂alkoxy, aryl,aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl,heteroaryloxy, heteroaralkoxy, acyl, acyloxy, hydroxyC₁₋₁₂alkyl, amino,acylamino, C₁₋₁₂alkyl-amino, arylamino, aralkylamino, aminoC₁₋₁₂alkyl,C₁₋₁₂alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl,C₁₋₁₂alkoxyC₁₋₁₂alkyl, aryloxyC₁₋₁₂alkyl, aralkoxyC₁₋₁₂alkyl,C₁₋₁₂alkylthio, thioC₁₋₁₂alkyl, C₁₋₁₂alkoxycarbonylamino,aryloxycarbonylamino, aralkoxycarbonylamino, —COR¹¹, or —SO₂R¹², whereinR¹¹ and R¹² independently of each other are selected from hydroxy,halogen, perhalomethyl, C₁₋₆alkoxy or amino optionally substituted withone or more C₁₋₆alkyl, perhalomethyl or aryl; optionally substitutedwith one or more halogen, perhalomethyl, hydroxy, nitro or cyano;

[0013] ring B fused to the ring containing X and N represents a 5-6membered cyclic ring, optionally substituted with one or more halogen,perhalomethyl, hydroxy, nitro, cyano, formyl, or C₁₋₁₂alkyl,C₄₋₁₂-alkenynyl, C₂₋₁₂-alkenyl, C₂₋₁₂-alkynyl, C₁₋₁₂alkoxy, aryl,aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl,heteroaryloxy, heteroaralkoxy, acyl, acyloxy, hydroxyC₁₋₁₂alkyl, amino,acylamino, C₁₋₁₂alkyl-amino, arylamino, aralkylamino, aminoC₁₋₁₂alkyl,C₁₋₁₂alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl,C₁₋₁₂alkoxyC₁₋₁₂alkyl, aryloxyC₁₋₁₂alkyl, aralkoxyC₁₋₁₂alkyl,C₁₋₁₂alkylthio, thioC₁₋₁₂alkyl, C₁₋₁₂alkoxycarbonylamino,aryloxycarbonylamino, aralkoxycarbonylamino, —COR¹¹, or —SO₂R¹², whereinR¹¹ and R¹² independently of each other are selected from hydroxy,halogen, perhalomethyl, C₁₋₆alkoxy or amino optionally substituted withone or more C₁₋₆alkyl, perhalomethyl or aryl; optionally substitutedwith one or more halogen, perhalomethyl, hydroxy, nitro or cyano;

[0014] X is a valence bond, —(CHR⁹)—, —(CHR⁹)—CH₂—, —CH═CH—, —O—,—O—(CHR⁹)—, —S—(CHR⁹)—, —(NR⁹—CH₂—, —(CHR⁹)—CH═CH—,—(CHR⁹)—CH₂—CH₂—,—(C═O)—, —O—CH₂—O—, —(NR⁹)—, —(NR⁹)—S(O₂)—, —CH═(CR⁹)—,—(CO)—(CHR⁹)—, —CH₂—(SO)—, —S—, —(SO)—, —(SO₂)—, —CH₂—(SO₂)—,—CH₂—O—CH₂—, wherein R⁹ is hydrogen, halogen, hydroxy, nitro, cyano,formyl, C₁₋₁₂alkyl, C₁₋₁₂alkoxy, aryl, aryloxy, aralkyl, aralkoxy,heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy,acyl, acyloxy, hydroxyalkyl, amino, acylamino, C₁₋₁₂alkyl-amino,arylamino, aralkylamino, aminoC₁₋₁₂alkyl, C₁₋₁₂alkoxycarbonyl,aryloxycarbonyl, aralkoxycarbonyl, C₁₋₁₂alkoxyC₁₋₁₂alkyl,aryloxyC₁₋₁₂alkyl, aralkoxyC₁₋₁₂alkyl, C₁₋₁₂alkylthio, thioC₁₋₁₂alkyl,C₁₋₁₂alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino,—COR¹¹, or —SO₂R¹², wherein R¹¹ and R¹² independently of each other areselected from hydroxy, halogen, C₁₋₆alkoxy, amino optionally substitutedwith one or more C₁₋₆alkyl, perhalomethyl or aryl; Q is —O—, —S—, >SO₂,>NR¹³, wherein R¹³ is hydrogen or C₁₋₆alkyl, Ar represents arylene,heteroarylene, or a divalent heterocyclic group optionally substitutedwith one or more C₁₋₆alkyl or aryl; R⁵ represents hydrogen, hydroxy,halogen, C₁₋₁₂alkoxy, C₁₋₁₂alkyl, C₄₋₁₂-alkenynyl, C₂₋₁₂-alkenyl,C₂₋₁₂-alkynyl or aralkyl; optionally substituted with one or morehalogen, perhalomethyl, hydroxy, nitro or cyano; or R⁵ forms a bondtogether with R⁶, R⁶ represents hydrogen, hydroxy, halogen, C₁₋₁₂alkoxy,C₁₋₁₂alkyl, C₄₋₁₂alkenynyl, C₂₋₁₂-alkenyl, C₂₋₁₂-alkynyl, acyl oraralkyl; optionally substituted with one or more halogen, perhalomethyl,hydroxy, nitro or cyano; or R⁶ forms a bond together with R⁵, R⁷represents hydrogen, C₁₋₁₂alkyl, C₄₋₁₂-alkenynyl, C₂₋₁₂-alkenyl,C₂₋₁₂-alkynyl, aryl, aralkyl, C₁₋₁₂alkoxyC₁₋₁₂alkyl,C₁₋₁₂alkoxycarbonyl, aryloxycarbonyl, C₁₋₁₂alkylaminocarbonyl,arylaminocarbonyl, acyl, heterocyclyl, heteroaryl or heteroaralkylgroups; optionally substituted with one or more halogen, perhalomethyl,hydroxy, nitro or cyano; R⁸ represents hydrogen, C₁₋₁₂alkyl,C₄₋₁₂-alkenynyl, C₂₋₁₂-alkenyl, C₂₋₁₂-alkynyl, aryl, aralkyl,heterocyclyl, heteroaryl or heteroaralkyl groups; optionally substitutedwith one or more halogen, perhalomethyl, hydroxy, nitro or cyano; Yrepresents oxygen, sulphur or NR¹⁰, where R¹⁰ represents hydrogen,C₁₋₁₂alkyl, aryl, hydroxyC₁₋₁₂alkyl or aralkyl groups or when Y is NR¹⁰,R⁸ and R¹⁰ may form a 5 or 6 membered nitrogen containing ring,optionally substituted with one or more C₁₋₆alkyl; n is an integerranging from I to 4 and m is an integer ranging from 0 to 1, providedthat A or B does not represent phenyl; or a pharmaceutically acceptablesalt thereof.

[0015] In a preferred embodiment, the present invention is concernedwith compounds of formula I wherein ring A fused to the ring containingX and N represents a 5-6 membered cyclic ring, optionally substitutedwith one or more hydrogen, halogen, perhalomethyl, hydroxy, cyano, orC₁₋₇alkyl, C₄₋₇-alkenynyl, C₂₋₇-alkenyl, C₂₋₇-alkynyl, C₁₋₇alkoxy, aryl,aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl,heteroaryloxy, heteroaralkoxy, acyl, acyloxy, hydroxyC₁₋₇alkyl, amino,acylamino, C₁₋₇alkyl-amino, arylamino, aralkylamino, aminoC₁₋₇alkyl,C₁₋₇alkoxyC₁₋₇alkyl, aryloxyC₁₋₇alkyl, aralkoxyC₁₋₇alkyl, C₁₋₇alkylthio,thioC₁₋₇alkyl, C₁₋₇alkoxycarbonylamino, aryloxycarbonylamino,aralkoxycarbonylamino, —COR¹¹, or —SO₂R¹², wherein R¹¹ and R¹²independently of each other are selected from hydroxy, perhalomethyl oramino optionally substituted with one or more C₁₋₆alkyl, perhalomethylor aryl; optionally substituted with one or more halogen, perhalomethyl,hydroxy cyano;

[0016] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein ring A fused to the ringcontaining X and N represents a 5-6 membered cyclic ring, optionallysubstituted with one or more hydrogen, halogen, perhalomethyl, hydroxy,cyano, or C₁₋₇alkyl, C₄₋₇-alkenynyl, C₂₋₇-alkenyl, C₂₋₇-alkynyl,C₁₋₇alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl,heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, amino, acylamino,C₁₋₇alkyl-amino, arylamino, aralkylamino, aminoC₁₋₇alkyl,C₁₋₇alkoxyC₁₋₇alkyl, aryloxyC₁₋₇alkyl, aralkoxyC₁₋₇alkyl, C₁₋₇alkylthio,thioC₁₋₇alkyl; optionally substituted with one or more halogen orhydroxy;

[0017] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein ring A fused to the ringcontaining X and N represents a 5-6 membered cyclic ring, optionallysubstituted with one or more hydrogen, halogen, perhalomethyl, hydroxyor C₁₋₇alkyl, C₂₋₇-alkenyl, C₂₋₇-alkynyl, C₁₋₇alkoxy, aryl, aryloxy,aralkyl, aralkoxy, heteroaryl, heteroaryloxy, heteroaralkoxy, acyl,arylamino, aryloxyC₁₋₇alkyl.

[0018] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein ring A fused to the ringcontaining X and N represents a 5-6 membered cyclic ring, optionallysubstituted with one or more hydrogen, halogen, perhalomethyl, hydroxyor C₁₋₇alkyl, C₂₋₇-alkenyl, C₂₋₇-alkynyl, C₁₋₇alkoxy or aryl.

[0019] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein ring A fused to the ringcontaining X and N represents a 5-6 membered cyclic ring, optionallysubstituted with one or more hydrogen or halogen.

[0020] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein ring B fused to the ringcontaining X and N represents a 5-6 membered cyclic ring, optionallysubstituted with one or more hydrogen, halogen, perhalomethyl, hydroxy,cyano, or C₁₋₇alkyl, C₄₋₇alkenynyl, C₂₋₇-alkenyl, C₂₋₇-alkynyl,C₁₋₇alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl,heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, acyloxy,hydroxyC₁₋₇alkyl, amino, acylamino, C₁₋₇alkyl-amino, arylamino,aralkylamino, aminoC₁₋₇alkyl, C₁₋₇alkoxyC₁₋₇alkyl, aryloxyC₁₋₇alkyl,aralkoxyC₁₋₇alkyl, C₁₋₇alkylthio, thioC₁₋₇alkyl,C₁₋₇alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino,—COR¹¹, or —SO₂R¹², wherein R¹¹ and R¹² independently of each other areselected from hydroxy, perhalomethyl or amino optionally substitutedwith one or more C₁₋₆alkyl, perhalomethyl or aryl; optionallysubstituted with one or more halogen, perhalomethyl, hydroxy or cyano.

[0021] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein ring B fused to the ringcontaining X and N represents a 5-6 membered cyclic ring, optionallysubstituted with one or more hydrogen, halogen, perhalomethyl, hydroxy,cyano, or C₁₋₇alkyl, C₄₋₇-alkenynyl, C₂₋₇-alkenyl, C₂₋₇-alkynyl,C₁₋₇alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl,heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, amino, acylamino,C₁₋₇alkyl-amino, arylamino, aralkylamino, aminoC₁₋₇alkyl,C₁₋₇alkoxyC₁₋₇alkyl, aryloxyC₁₋₇alkyl, aralkoxyC₁₋₇alkyl, C₁₋₇alkylthio,thioC₁₋₇alkyl; optionally substituted with one or more halogen orhydroxy.

[0022] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein ring B fused to the ringcontaining X and N represents a 5-6 membered cyclic ring, optionallysubstituted with one or more hydrogen, halogen, perhalomethyl, hydroxyor C₁₋₇alkyl, C₂₋₇-alkenyl, C₂₋₇alkynyl, C₁₋₇alkoxy, aryl, aryloxy,aralkyl, aralkoxy, heteroaryl, heteroaryloxy, heteroaralkoxy, acyl,arylamino, aryloxyC₁₋₇alkyl.

[0023] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein ring B fused to the ringcontaining X and N represents a 5-6 membered cyclic ring, optionallysubstituted with one or more hydrogen, halogen, perhalomethyl, hydroxyor C₁₋₇alkyl, C₂₋₇alkenyl, C₂₋₇alkynyl, C₁₋₇alkoxy or aryl.

[0024] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein ring B fused to the ringcontaining X and N represents a 5-6 membered cyclic ring, optionallysubstituted with one or more hydrogen or halogen.

[0025] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein X is a valence bond,—(CHR⁹)—, —(CHR⁹)—CH₂—, —CH═CH—, —O—, —O—(CHR⁹)—, —S—(CHR⁹)—,—(NR⁹)—CH₂—, —(CHR⁹)—CH═CH—, —(CHR⁹)—CH₂—CH₂—, —(C═O)—, —O—CH₂—O—,—(NR⁹)—, —(NR⁹)—S(O₂)—, —CH═(CR⁹)—, —(CO)—(CHR⁹)—, —CH₂—(SO)—, —S—,—(SO)—, —(SO₂)—, —CH₂—(SO₂)—, —CH₂—O—CH₂—, wherein R⁹ is hydrogen,halogen, hydroxy, cyano, C₁₋₇alkyl, C₁₋₇alkoxy, aryl, aryloxy, aralkyl,aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy,heteroaralkoxy, acyl, acyloxy, hydroxyalkyl, amino, acylamino,C₁₋₇alkyl-amino, arylamino, aralkylamino, aminoC₁₋₇alkyl,C₁₋₇alkoxyC₁₋₇alkyl, aryloxyC₁₋₇alkyl, aralkoxyC₁₋₇alkyl, C₁₋₇alkylthio,thioC₁₋₇alkyl.

[0026] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein X is a valence bond,—(CHR⁹)—, —(CHR⁹)—CH₂—, —CH═CH—, —O—, —O—(CHR⁹)—, —S—(CHR⁹)—,—(NR⁹)—CH₂—, —(CHR⁹)—CH═CH—, —(CHR⁹)—CH₂—CH₂—, —(C═O)—, —O—CH₂—O—,—(NR⁹)—, —(NR⁹)—S(O₂)—, —CH═(CR⁹)—, —(CO)—(CHR⁹)—, —CH₂—(SO)—, —S—,—(SO)—, —(SO₂)—, —CH₂—(SO₂)—, —CH₂—O—CH₂—, wherein R⁹ is hydrogen,halogen, hydroxy, C₁₋₇alkyl, C₁₋₇alkoxy, aryl.

[0027] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein X is a valence bond,—(CHR⁹)—, —(CHR⁹)—CH₂—, —CH═CH—, —O—(CHR⁹)—, —S—(CHR⁹)—, —(NR⁹)—CH₂—,—(CHR⁹)—CH═CH—, —(CHR⁹)—CH₂—CH₂—, —(C═O)—, —O—CH₂—O—, —(NR⁹)—S(O₂)—,—CH═(CR₉)—, —(CO)—(CHR⁹)—, —CH₂—(SO)—, —(SO)—, —(SO₂)—, —CH₂—(SO₂)—,—CH₂—O—CH₂—, wherein R⁹ is hydrogen, halogen, hydroxy, C₁₋₄alkyl,C₁₋₄alkoxy.

[0028] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein X is a valence bond,—(CHR⁹)—, —(CHR⁹)—CH₂—, —CH═CH—, —O—(CHR⁹)—, —(CHR⁹)—CH═CH—,—(CHR⁹)—CH₂—CH₂—, —(C═O)—, —O—CH₂—O—, —CH═(CR⁹)—, —(CO)—(CHR⁹)—,—CH₂—(SO)—, —(SO)—, —(SO₂)—, —H₂—(O₂)—C—CH₂—O—CH₂—H wherein R⁹ ishydrogen.

[0029] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein Q is —O— or —S—.

[0030] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein Q is —O—.

[0031] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein Ar represents arylene,heteroarylene, or a divalent heterocyclic group optionally substitutedwith one or more C₁₋₆alkyl or aryl; R⁵ represents hydrogen, hydroxy,halogen, C₁₋₇alkoxy, C₁₋₇alkyl, C₄₋₇-alkenynyl, C₂₋₇-alkenyl, C₂₋₇; orR⁵ forms a bond together with R⁶, R⁶ represents hydrogen, hydroxy,halogen, C₁₋₇alkoxy, C₁₋₇alkyl, C₄₋₇-alkenynyl, C₂₋₇-alkenyl,C₂₋₇alkynyl; or R⁶ forms a bond together with R⁵, R⁷ representshydrogen, C₁₋₇alkyl, C₄₋₇-alkenynyl, C₂₋₇-alkenyl, C₂₋₇-alkynyl, aryl,aralkyl, C₁₋₇alkoxyC₁₋₇alkyl, C₁₋₇alkoxycarbonyl, aryloxycarbonyl,C₁₋₇alkylaminocarbonyl, arylaminocarbonyl, acyl, heterocyclyl,heteroaryl or heteroaralkyl groups; R⁸ represents hydrogen, C₁₋₇alkyl,C₄₋₇alkenynyl, C₂₋₇-alkenyl, C₂₋₇-alkynyl, aryl, aralkyl, heterocyclyl,heteroaryl or heteroaralkyl; Y represents oxygen, sulphur or NR¹⁰, whereR¹⁰ represents hydrogen, C₁₋₇alkyl, hyrdroxyC₁₋₇alkyl; n is an integerranging from 2 to 3 and m is an integer ranging from 0 to 1.

[0032] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein Ar represents arylene orheteroarylene; R⁵ represents hydrogen, hydroxy, halogen; or R⁵ forms abond together with R⁶, R⁶ represents hydrogen, hydroxy, halogen; or R⁶forms a bond together with R⁵, R⁷ represents hydrogen, C₁₋₇alkyl,C₂₋₇-alkenyl, C₂₋₇-alkynyl, aryl, aralkyl, C₁₋₇alkoxyC₁₋₇alkyl,C₁₋₇alkylaminocarbonyl, arylaminocarbonyl, acyl, heterocyclyl,heteroaryl or heteroaralkyl groups; R⁸ represents hydrogen, C₁₋₇alkyl,C₂₋₇-alkenyl, C₂₋₇alkynyl,; Y represents oxygen or sulphur; n is aninteger ranging from 2 to 3 and m is 1.

[0033] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein Ar represents arylene orheteroarylene; R⁵ represents hydrogen. R⁶ represents hydrogen; R⁷represents hydrogen, C₁₋₇alkyl, C₂₋₇-alkenyl, C₂₋₇-alkynyl, aryl,aralkyl, C₁₋₇alkoxyC₁₋₇alkyl; R⁸ represents hydrogen, C₁₋₇alkyl,C₂₋₇-alkenyl, C₂₋₇-alkynyl,; Y represents oxygen; n is an integerranging from 2 to 3 and m is 1.

[0034] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein Ar represents arylene; R⁵represents hydrogen; R⁶ represents hydrogen; R⁷ represents hydrogen,C₁₋₄alkyl, C₂₋₄-alkenyl, C₂₋₄-alkynyl, R⁸ represents hydrogen,C₁₋₄alkyl, Y represents oxygen; n is an integer ranging from 2 to 3 andm is 1.

[0035] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein Ar represents phenylene;R⁵ represents hydrogen; R⁶ represents hydrogen; R⁷ represents hydrogen,C₁₋₄alkyl, R⁸ represents hydrogen Y represents oxygen; n is an integerranging from 2 to 3 and m is 1.

[0036] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein A is 5 membered cyclicring containing S.

[0037] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein B is 5 membered cyclicring containing S.

[0038] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein X is —CH═(CR⁹)—, whereinR⁹ is H.

[0039] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein n is 2.

[0040] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein Q is —O—.

[0041] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein m is 1.

[0042] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein Ar is phenylene.

[0043] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein R⁵ is H.

[0044] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein R⁶ is H.

[0045] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein R⁷ is ethyl.

[0046] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein Y is oxygen.

[0047] In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein R⁸ is H.

[0048] Preferred compounds of the invention are:

[0049]3-{4-[2-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)-ethoxy]-phenyl}2-ethoxy-propionicacid,

[0050]3-{4-[2-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)-ethoxy]-phenyl}-2-methoxy-propionicacid,

[0051]3-{4-[2-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)-ethoxy]-phenyl}-2-propoxy-propionicacid,

[0052]3-{4-[2-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)-ethoxy]-phenyl}-2-benzyloxy-propionicacid,

[0053]3-{4-[2-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)-ethyl]-phenyl}2-ethoxy-propionicacid,

[0054]3-{4-[2-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)-ethyl]-phenyl}-2-methoxy-propionicacid,

[0055]3-{4-[2-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)-ethyl]-phenyl}-2-propoxy-propionicacid,

[0056]3-{4-[2-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)-ethyl]-phenyl}-2-benzyloxy-propionicacid,

[0057]3-{4-[1-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)-methoxy]-phenyl}-2-ethoxy-propionicacid,

[0058]3-{4-[1-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen4-yl)-methoxy]-phenyl}-2-methoxy-propionicacid,

[0059]3-{4-[1-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen4-yl)-methoxy]-phenyl}-2-benzyloxy-propionicacid,

[0060]3-{4-[3-(8,9-Dihydro-3,5-dithia4-aza-cyclopenta[f]azulen-4-yl)-propoxy]-phenyl}-2-ethoxy-propionicacid,

[0061]3-{4-[3-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)-propoxy]-phenyl}2-methoxy-propionicacid,

[0062]3-{4-[3-(8,9-Dihydro-3,5-dithia4-aza-cyclopenta[f]azulen-4-yl)-propoxy]-phenyl}-2-benzyloxy-propionicacid,

[0063]3-{4-[3-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)-propyl]-phenyl}-2-ethoxy-propionicacid,

[0064]3-{4-[3-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen4-yl)-propyl]-phenyl}2-methoxy-propionicacid,

[0065]3-{4-[3-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen4-yl)-propyl]-phenyl}2-benzyloxy-propionicacid,

[0066] 2-Ethoxy-3-(4-(2-(9H-1, 8,10-triaza-anthracen-10-yl)-ethoxy)-phenyl)-propionic acid,

[0067] 2-methoxy-3-(4-(2-(9H-1, 8,10-triaza-anthracen-10-yl)-ethoxy)-phenyl)-propionic acid,

[0068] 2-propoxy-3-(4-(2-(9H-1, 8,10-triaza-anthracen-10-yl)-ethoxy)-phenyl)-propionic acid,

[0069] 2-benzyloxy-3-(4-(2-(9H-1, 8,10-triaza-anthracen-10-yl)-ethoxy)-phenyl)-propionic acid,

[0070] 2-ethoxy-3-(4-(1 -(9H-1, 8,10-triaza-anthracen-10-yl)-methoxy)-phenyl)-propionic acid,

[0071] 2-methoxy-3-(4-(1 -(9H-1, 8,10-triaza-anthracen-10-yl)-methoxy)-phenyl)-propionic acid,

[0072] 2-benzyloxy-3-(4-(1 -(9H-1, 8,10-triaza-anthracen-10-yl)-methoxy)-phenyl)-propionic acid,

[0073] 2-ethoxy-3-(4-(3-(9H-1, 8,10-triaza-anthracen-10-yl)-propoxy)-phenyl)-propionic acid,

[0074] 2-propoxy-3-(4-(3-(9H-1, 8,10-triaza-anthracen-10-yl)-propoxy)-phenyl)-propionic acid,

[0075] 2-methoxy-3-(4-(3-(9H-1, 8,10-triaza-anthracen-10-yl)-propoxy)-phenyl)-propionic acid,

[0076] 2-benzyloxy-3-(4-(3-(9H-1, 8,10-triaza-anthracen-10-yl)-propoxy)-phenyl)-propionic acid,

[0077] 2-ethoxy-3-(4-(3-(9H-1, 8,10-triaza-anthracen-10-yl)-propyl)-phenyl)-propionic acid,

[0078] 2-propoxy-3-(4-(3-(9H-1, 8,10-triaza-anthracen-10-yl)-propyl)-phenyl)-propionic acid,

[0079] 2-methoxy-3-(4-(3-(9H-1, 8,10-triaza-anthracen-10-yl)-propyl)-phenyl)-propionic acid,

[0080] 2-benzyloxy-3-(4-(3-(9H-1, 8,10-triaza-anthracen-10-yl)-propyl)-phenyl)-propionic acid,

[0081] 2-ethoxy-3-(4-(2-(4, 5,9-triaza-fluoren-9-yl)-ethoxy)-phenyl)-propionic acid,

[0082] 2-methoxy-3-(4-(2-(4, 5,9-triaza-fluoren-9-yl)-ethoxy)-phenyl)-propionic acid,

[0083] 2-propoxy-3-(4-(2-(4, 5,9-triaza-fluoren-9-yl)-ethoxy)-phenyl)-propionic acid,

[0084] 2-ethoxy-3-(4-(1-(4, 5,9-triaza-fluoren-9-yl)-methoxy)-phenyl)-propionic acid,

[0085] 2-methoxy-3-(4-(1-(4, 5,9-triaza-fluoren-9-yl)-methoxy)-phenyl)-propionic acid,

[0086] 2-benzyoxy-3-(4-(1-(4, 5,9-triaza-fluoren-9-yl)-methoxy)-phenyl)-propionic acid,

[0087] 2-ethoxy-3-(4-(3-(4, 5,9-tiaza-fluoren-9-yl)-propoxy)-phenyl)-propionic acid,

[0088] 2-methoxy-3-(4-(3-(4, 5,9-triaza-fluoren-9-yl)-propoxy)-phenyl)-propionic acid,

[0089] 2-benzyloxy-3-(4-(3-(4, 5,9-triaza-fluoren-9-yl)-propoxy)-phenyl)-propianic acid,

[0090] 2-propoxy-3-(4-(3-(4, 5,9-triaza-fluoren-9-yl)-propoxy)-phenyl)-propionic acid,

[0091] 2-ethoxy-3-(4-(3-(4, 5,9-triaza-fluoren-9-yl)-propyl)-phenyl)-propionic acid,

[0092] 2-methoxy-3-(4-(3-(4, 5,9-triaza-fluoren-9-yl)-propyl)-phenyl)-propionic acid,

[0093] 2-propoxy-3-(4-(3-(4, 5,9-triaza-fluoren-9-yl)-propyl)-phenyl)-propionic acid,

[0094] 2-ethoxy-3-(4-(2-(1, 8,9-triaza-fluoren-9-yl)-ethoxy)-phenyl)-propionic acid,

[0095] 2-methoxy-3-(4-(2-(1, 8,9triaza-fluoren-9-yl)-ethoxy)-phenyl)-propionic acid,

[0096] 2-propoxy-3-(4-(2-(1, 8,9-triaza-fluoren-9-yl)-ethoxy)-phenyl)-propionic acid,

[0097] 2-betnzyoxy-3-(4-(2-(1, 8,9-triaza-fluoren-91yl)-ethoxy)-phenyl)-propionic acid,

[0098] 2-ethoxy-3-(4-(1-(1, 8,9-triaza-fluoren-9-yl)-methoxy)-phenyl)-propionic acid,

[0099] 2-ethoxy-3-(4-(1-(1, 8,9-triaza-fluoren-9-yl)-methoxy)-phenyl)-propionic acid,

[0100] 2-propoxy-3-(4-(1-(1, 8,9-triaza-fluoren-9-yl)-methoxy)-phenyl)-propionic acid,

[0101] 2-benzyloxy-3-(4-(1-(1, 8,9-triaza-fluoren-9-yl)-methoxy)-phenyl)propionic acid,

[0102] 2-ethoxy-3-(4-(3-(1, 8,9-triaza-fluoren-9-yl)-propoxy)-phenyl)-propionic acid,

[0103] 2-ethoxy-3-(4-(3-(1, 8,9-triaza-fluoren-9-yl)-propoxy)-phenyl)-propionic acid,

[0104] 2-propoxy-3-(4-(3-(1, 8,9-triaza-fluoren-9-yl)-propoxy)phenyl)propionic acid,

[0105] 2-benzyloxy-3-(4-(3-(1, 8,9-triaza-fluoren-9-yl)-propoxy)-phenyl)-propionic acid,

[0106] 2-ethoxy-3-(4-(3-(1, 8,9-triaza-fluoren-9-yl)-propyl)-phenyl)-propionic acid,

[0107] 2-methoxy-3-(4-(3-(1, 8,9-triaza-fluoren-9-yl)-propyl)-phenyl)-propionic acid,

[0108] 2-propoxy-3-(4-(3-(1, 8,9-triaza-fluoren-9-yl)-propyl)-phenyl)-propionic acid,

[0109] 2-benzyloxy-3-(4-(3-(1, 8,9-triaza-fluoren-9-yl)-propyl)-phenyl)-propionic acid,

[0110] 3-(4-(2-(dithieno[2,3-b; 3′,2′-d]pyrrol-7-yl)-ethoxy)-phenyl)-2-ethoxypropionic acid,

[0111] 2-metho[2,3-b;3′, 2′-d]pyrrol-7-yl)-etoxy)-phenyl) -propionicacid,

[0112] 3(4-(2-d(dithieno[2,3-3′,2′-d]pryrrol-7-yl)-ethoxy)-phenyl)2-propionic acid,

[0113] 3-(4-(2-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)-ethoxy)-phenyl)-2-benzyloxy-propionic acid,

[0114] 3-(4-(1-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)-ethoxy)-phenyl)-2-methoxy-propionic acid,

[0115] 3-(4-(1-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)-methoxy)-phenyl)-2-ethoxy-propionic acid,

[0116] 3-(4-(1-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)-methoxy)-phenyl)-2-propoxy-propionic acid,

[0117] 3-(4-(1-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)-methoxy)-phenyl)-2-benzytoxy-propionic acid,

[0118] 3-(4-(3-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)-propoxy)-phenyl)-2-ethoxy-propionic acid,

[0119] 3-(4-(3-(dithieno[2,3-b; 3′,2′-d]pyrrol-7-yl)-propoxy)-phenyl)-2-methoxy-propionic acid,

[0120] 3-(4-(3-(dithieno[2,3-b;3′, 240-d]pyrrol-7-yl)-propoxy)-phenyl)-2-propoxy-propionic acid,

[0121] 3-(4-(3-(dithieno[2,3-b; 3′,2′-d]pyrrol-7-yl)-propoxy)-phenyl)-2-benzytoxy-propionic acid,

[0122] 3-(4-(3-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)-propyl)-phenyl)-2-ethoxy-propionic acid,

[0123] 3-(4-(3-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)-propyl)-phenyl)-2-methoxy-propionic acid,

[0124] 3-(4-(3-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)-propyl)-phenyl)-2-bezyoxy-propionic acid,

[0125] 3-(4-(2-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)-ethoxy)phenyl)-2-ethoxy-propionic acid,

[0126] 3-(4-(2-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)-ethoxy)-phenyl)-2-ethoxy-propionic acid,

[0127] 3-(4-(1-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)-methoxy)-phenyl)-2-ethoxy-propionic acid,

[0128] 3-(4-(1-(difurano[2,3-b;3′,2′-d]pyrol-7-yl)-ethoxy)-phenyl)-2-methoxy-propionic acid,

[0129] 3-(4-(1-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)-ethoxy)-phenyl)-2-propoxy-propionic acid,

[0130] 3-(4-(1-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)-methoxy)-phenyl)-2-benzyloxy-propionic acid,

[0131] 3-(4-(3-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)-propoxy)-phenyl)-2-ethoxy-propionic acid,

[0132] 3-(4-(3-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)-propoxy)-phenyl)-2-propoxy-propionic acid,

[0133] 3-(4-(3-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)-propoxy)-phenyl)-2-methoxy-propionic acid,

[0134] 3-(4-(3-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)-propoxy)-phenyl)-2-benzyloxy-propionic acid,

[0135] 3-(4-(3-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)-propy)-phenyl)-2-etoxy-propionic acid,

[0136] 3-(4-(3-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)-propy)-phenyl)-2-propoxy-propionic acid,

[0137] 3-(4-(3-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)-propyl)-phenyl)-2-methoxy-propionic acid,

[0138] 3-(4-(3-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)-propyl)-phenyl)-2-benzyloxy-propionic acid,

[0139]3-(4-(2-(4H-1,7-dithia-8-aza-s-indacen-8-yl)-ethoxy)-phenyl)-2-ethoxy-propionicacid,

[0140]3-(4-(2-(4H-1,7-dithia-8-aza-s-indacen-8-yl)-ethoxy)-phenyl)-2-methoxy-propionicacid,

[0141]3-(4-(2-(4H-1,7-dithia-8-aza-s-indacen-8-yl)-ethoxy)-phenyl)-2-propoxy-propionicacid,

[0142] 3-(4-(2-(4H-1,7-dithia-8-aza-s-indacen-8-yl)-ethoxy)-pheny)-2-ethoxy-propionicacid,

[0143]3-(4-(2-(4H-1,7-dithia-8-aza-s-indacen-8-yl)-methoxy)-phenyl)-2-ethoxy-propionicacid,

[0144]3-(4-(1-(4H-1,7-dithia-8-aza-s-indacen-8-yl)-methoxy)-phenyl)-2-methoxy-propionicacid,

[0145]3-(4-(2-(4H-1,7-dithia-8-aza-s-indacen-8-yl)-methoxy)-pheny)1-2-propoxy-propionicacid,

[0146] 3-(4-(1-(4H-1,7-dithia-8-aza-s-indacen-8-yl)-methoxy)-phenyl)-2-ethoxy-prop ionicacid,

[0147]3-(4-(3-(4H-1,7-dithia-8-aza-s-indacen-8-yl)-propoxy)-phenyl)-2-ethoxy-propionicacid,

[0148] 3-(4-(3-(4H-1,7-dithia8-aza-s-indacen-8-yl)-propoxy)-phenyl)-2-methoxy-propionic acid,

[0149]3-(4-(3-(4H-1,7-dithia-8-aza-s-indacen-8-yl)-propoxy)-phenyl)-2-propoxy-propionicacid,

[0150]3-(4-(3-(4H-1,7-dithia-8-aza-s-indacen-8-yl)-propoxy)-phenyl)-2-benzyloxy-propionicacid,

[0151]3-(4-(3-(4H-1,7-dithia-8-aza-s-indacen-8-yl)-propyl)-phenyl)-2-ethoxy-propionicacid,

[0152]3-(4-(3-(4H-1,7-dithia-8-aza-s-indacen-8-yl)-propyl)-phenyl)-2-methoxy-propionicacid,

[0153]3-(4-(3-(4H-1,7-dithia-8-aza-s-indacen-8-yl)-propyl)-phenyl)-2-propoxy-propionicacid,

[0154]3-(4-(3-(4H-1,7-dithia-8-aza-s-indacen-8-yl)-propyl)-phenyl)-2-benzyloxy-propionicacid,

[0155]2-ethoxy-3-(4-(2-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)-ethoxy)-phenyl)-propionicacid,

[0156]2-methoxy-3-(4-(2-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)-ethoxy)-phenyl)-propionicacid,

[0157]2-propoxy-3-(4-(2-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)-ethoxy)-phenyl)-propionicacid,

[0158]2-propoxy-3-(4-(2-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)-ethoxy)-phenyl)-propionicacid,

[0159]2-benzyloxy-3-(4-(2-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)-ethoxy)-phenyl)-propionicacid,

[0160]2-ethoxy-3-(4-(1-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)-methoxy)-phenyl)-propionicacid,

[0161]2-methoxy-3-(4-(1-(4-oxa-1,₁7-dithia-8-aza-s-indacen-8-yl)-methoxy)-phenyl)-propionicacid,

[0162] 2-propoxy-3-(4-(1-(4-oxa-1,7) acid,

[0163]2-benzyloxy-3-(4-(1-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)-methoxy)-phenyl)-propionicacid,

[0164]2-ethoxy-3-(4-(3-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)-propoxy)-phenyl)-propionicacid,

[0165]2-methoxy-3-(4-(3-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)-propoxy)-phenyl)-propionicacid,

[0166]2-propoxy-3-(4-(3-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)-propoxy)-phenyl)-propionicacid,

[0167]2-benzyloxy-3-(4-(3-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)-propoxy)-phenyl)-propionicacid,

[0168]2-ethoxy-3-(4-(3-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)-propyl)-phenyl)-propionicacid,

[0169]2-ethoxy-3-(4-(3-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)-propyl)-phenyl)-propionicacid,

[0170]2-propoxy-3-(4-(3-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)-propyl)-phenyl)-propionicacid,

[0171] 2-benzyloxy-3-(4-(3-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)-propyl)-phenyl)-propionic acid;

[0172] or a pharmaceutically acceptable salt thereof.

[0173] A further preferred compound of the invention is:

[0174]3-{4-[2-*8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]-azulen-4-yl)-ethoxy]-phenyl}-2-ethoxy-propionicacid;

[0175] or a pharmaceutically acceptable salt thereof.

[0176] In the above structural formulas and throughout the presentspecification, the following terms have the indicated meaning:

[0177] The terms “C₁₋₁₂-alkyl” as used herein, alone or in combinationis intended to include those alkyl groups of the designated length ineither a linear or branched or cyclic configuration represents e.g.cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl andcyclooctyl and the like. Typical C₁₋₆-alkyl groups include, but are notlimited to, methyl, ethyl, n-propyl, iso-propyl, butyl, iso-butyl,sec-butyl, tert-butyl, pentyl, iso-pentyl, hexyl, iso-hexyl,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl andcyclooctyl and the like.

[0178] The terms “C_(2-n)-alkenyl” wherein n′ can be from 3 through 15,as used herein, represents an olefinically unsaturated branched orstraight group having from 2 to the specified number of carbon atoms andat least one double bond. Examples of such groups include, but are notlimited to, vinyl, 1-propenyl, 2-propenyl, allyl, iso-propenyl,1,3-butadienyl, 1-butenyl, hexenyl, pentenyl, and the like.

[0179] The terms “C_(2-n)-alkynyl” wherein n′ can be from 3 through 15,as used herein, represent an unsaturated branched or straight grouphaving from 2 to the specified number of carbon atoms and at least onetriple bond. Examples of such groups include, but are not limited to,1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 1-pentynyl, 2-pentynyl andthe like.

[0180] The terms “C_(4-n)-alkenynyl” wherein n′ can be from 5 through15,as used herein, represent an unsaturated branched or straighthydrocarbon group having from 4 to the specified number of carbon atomsand both at least one double bond and at least one triple bond. Examplesof such groups include, but are not limited to, 1-penten4-yne,3-penten-1-yne, 1,3-hexadiene-5-yne and the like.

[0181] The term “C₁₋₁₂-alkoxy” as used herein, alone or in combinationis intended to include those C₁₋₁₂-alkyl groups of the designated lengthin either a linear or branched or cyclic configuration linked thorugh anether oxygen having its free valence bond from the ether oxygen.Examples of linear alkoxy groups are methoxy, ethoxy, propoxy, butoxy,pentoxy and hexoxy. Examples of branched alkoxy are isoprpoxy,sec-butoxy, tert-butoxy, isopentoxy and isohexoxy. Example of cyclicalkoxy are cyclopropyloxy, cyclobutyloxy, cyclopentyloxy andcyclohexyloxy.

[0182] The term “C₁₋₆-alkoxycarbonyloxy” is intended to include theabove defined C₁₋₆-alkoxy groups attached to a carbonyloxy moiety, eg.methoxycarbonyloxy, ethoxycarbonyloxy, etc..

[0183] As used herein the term “C₄₋₁₂-(cycloalkylalkyl)” represents abranched or straight alkyl group substituted at a carbon with acycloalkyl group. Examples of such groups include, but are not limitedto, cyclopropylethyl, cyclobutylmethyl, 2-(cyclohexyl)ethyl,cyclohexylmethyl, 3-(cyclopentyl)-1-propyl, and the like.

[0184] The term “C₁₋₁₂-alkylthio” as used herein, alone or incombination, refers to a straight or branched or cyclic monovalentsubstituent comprising a C₁₋₁₂-alkyl group linked through a divalentsulfur atom having its free valence bond from the sulfur atom and having1 to 12 carbon atoms e.g. methylthio, ethylthio, propylthio, butylthio,pentylthio. Example of cyclic alkylthio are cyclopropylthio,cyclobutylthio, cyclopentylthio and cyclohexylthio.

[0185] The term “C₁₋₁₂alkylamino” as used herein, alone or incombination, refers to a straight or branched or cyclic monovalentsubstituent comprising a C₁₋₁₂-alkyl group linked through amino having afree valence bond from the nitrogen atom e.g. methylamino, ethylamino,propylamino, butylamino, pentylamino. Example of cyclic alkylamino arecyclopropylamino, cyclobutylamino, cyclopentylamino and cyclohexylamino.

[0186] The term “hydroxyC₁₋₁₂alkyl” as used herein, alone or incombination, refers to a C₁₋₁₂alkyl as defined herein whereto isattached a hydroxy group, e.g. hydroxyethyl, 1-hydroxypropyl,2-hydroxypropyl etc..

[0187] The term “arylamino” as used herein, alone or in combination,refers to an aryl as defined herein linked through amino having a freevalence bond from the nitrogen atom e.g. phenylamino, naphthylamino,etc..

[0188] The term “aralkylamino” as used herein, alone or in combination,refers to an aralkyl as defined herein linked through amino having afree valence bond from the nitrogen atom e.g. benzylamino,phenethylamino, 3-phenylpropylamino, 1-naphtylmethylamino,2-(1-naphtyl)ethylamino and the like.

[0189] The term “aminoC₁₋₁₂alkyl” as used herein, alone or incombination, refers to a C₁₋₁₂alkyl as defined herein whereto isattached an amino group, e.g. aminoethyl, 1-aminopropyl, 2-aminopropyletc..

[0190] The term “aryloxycarbonyl” as used herein, alone or incombination, refers to an aryloxy as defined herein linked through acarbonyl having a free valence bond from the carbon atom, e.g.phenoxycarbonyl, 1-naphthyloxycarbonyl or 2-naphthyloxycarbonyl, etc..

[0191] The term “aralkoxycarbonyl” as used herein, alone or incombination, refers to an aralkoxy as defined herein linked through acarbonyl having a free valence bond from the carbon atom, e.g.benzyloxycarbonyl, phenethoxycarbonyl, 3-phenylpropoxycarbonyl,1-naphthylmethoxycarbonyl, 2-(1-naphtyl)ethoxycarbonyl, etc..

[0192] The term “C₁₋₁₂alkoxyC₁₋₁₂alkyl” as used herein, alone or incombination, refers to a C₁₋₁₂alkyl as defined herein whereto isattached a C₁₋₁₂alkoxy as defined herein, e.g. methoxymethyl,ethoxymethyl, methoxyethyl, ethoxyethyl, etc..

[0193] The term “aryloxyC₁₋₁₂alkyl” as used herein, alone or incombination, refers to a C₁₋₁₂alkyl as defined herein whereto isattached an aryloxy as defined herein, e.g. phenoxymethyl,phenoxydodecyl, 1-naphthyloxyethyl, 2-naphthyloxypropyl, etc..

[0194] The term “aralkoxyC₁₋₁₂alkyl” as used herein, alone or incombination, refers to a C₁₋₁₂alkyl as defined herein whereto isattached an aralkoxy as defined herein, e.g. benzyloxymethyl,phenethoxydodecyl, 3-phenylpropoxyethyl, 1-naphthylmethoxypropyl,2-(1-naphtyl)ethoxymethyl, etc..

[0195] The term “thioC₁₋₁₂alkyl” as used herein, alone or incombination, refers to a C₁₋₁₂alkyl as defined herein whereto isattached a group of formula —SR′″ wherein R′″ is hydrogen, C₁₋₆alkyl oraryl, e.g. thiomethyl, methylthiomethyl, phenylthioethyl, etc..

[0196] The term “C₁₋₁₂alkoxycarbonylamino” as used herein, alone or incombination, refers to a C₁₋₁₂alkoxycarbonyl as defined herein linkedthrough amino having a free valence bond from the nitrogen atom e.g.methoxycarbonylamino, carbethoxyamino, propoxycarbonylamino,isopropoxycarbonylamino, n-butoxycarbonylamino,tert-butoxycarbonylamino, etc..

[0197] The term “aryloxycarbonylamino” as used herein, alone or incombination, refers to an aryloxycarbonyl as defined herein linkedthrough amino having a free valence bond from the nitrogen atom e.g.phenoxycarbonylamino, 1-naphthyloxycarbonylamino or2-naphthyloxycarbonylamino, etc..

[0198] The term “aralkoxycarbonylamino” as used herein, alone or incombination, refers to an aralkoxycarbonyl as defined herein linkedthrough amino having a free valence bond from the nitrogen atom e.g.benzyloxycarbonylamino, phenethoxycarbonylamino,3-phenylpropoxycarbonylamino, 1-naphthylmethoxycarbonylamino,2-(1-naphtyl)ethoxycarbonylamino, etc..

[0199] The term “aryl” is intended to include aromatic rings, such ascarboxylic aromatic rings selected from the group consisting of phenyl,naphthyl, (1-naphtyl or 2-naphtyl) optionally substituted with halogen,amino, hydroxy, C₁₋₆-alkyl or C₁₋₆-alkoxy.

[0200] The term “arylene” is intended to include divalent aromaticrings, such as carboxylic aromatic rings selected from the groupconsisting of phenylene, naphthylene, optionally substituted withhalogen, amino, hydroxy, C₁₋₆-alkyl or C₁₋₆alkoxy.

[0201] The term “halogen” means fluorine, chlorine, bromine or iodine.

[0202] The term “perhalomethyl” means trifluoromethyl, trichloromethyl,tribromomethyl or triiodomethyl.

[0203] The term “C₁₋₆-dialkylamino” as used herein refers to an aminogroup wherein the two hydrogen atoms independently are substituted witha straight or branched, saturated hydrocarbon chain having the indicatednumber of carbon atoms; such as dimethylamino, N-ethyl-N-methylamino,diethylamino, dipropylamino, N-(n-butyl)-N-methylamino,di(n-pentyl)amino, and the like.

[0204] The term “acyl” as used herein refers to a monovalent substituentcomprising a C₁₋₆-alkyl group linked through a carbonyl group; such ase.g. acetyl, propionyl, butyryl, isobutyryl, pivaloyl, valeryl, and thelike.

[0205] The term “acyloxy” as used herein refers to acyl as definedherein linked to an oxygen atom having its free valence bond from theoxygen atom e.g. acetyloxy, propionyloxy, butyryloxy, isobutyryloxy,pivaloyloxy, valeryloxy, and the like.

[0206] The term “C₁₋₁₂-alkoxycarbonyl” as used herein refers to amonovalent substituent comprising a C₁₋₁₂-alkoxy group linked through acarbonyl group; such as e.g. methoxycarbonyl, carbethoxy,propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl,sec-butoxycarbonyl, tert-butoxycarbonyl, 3-methylbutoxycarbonyl,n-hexoxycarbonyl and the like.

[0207] The term “a cyclic ring containing from 5 to 7 carbon atoms” asused herein refers to a monocyclic saturated or unsaturated or aromaticsystem, wherein the ring may be cyclopentyl, cyclopentenyl, cyclohexyl,phenyl or cycloheptyl.

[0208] The term “bicycloalkyl” as used herein refers to a monovalentsubstituent comprising a bicyclic structure made of 6-12 carbon atomssuch as e.g. 2-norbornyl, 7-norbornyl, 2-bicyclo[2. 2. 2]octyl and9-bicyclo[3. 3. 1]nonanyl.

[0209] The term “heteroaryl” as used herein, alone or in combination,refers to a monovalent substituent comprising a 5-6 membered monocyclicaromatic system or a 9-10 membered bicyclic aromatic system containingone or more heteroatoms selected from nitrogen, oxygen and sulfur, e.g.furan, thiophene, pyrrole, imidazole, pyrazole, triazole, pyridine,pyrazine, pyrimidine, pyridazine, isothiazole, isoxazole, oxazole,oxadiazole, thiadiazole, quinoline, isoquinoline, quinazoline,quinoxaline, indole, benzimidazole, benzofuran, pteridine and purine.

[0210] The term “heteroarylene” as used herein, alone or in combination,refers to a divalent group comprising a 5-6 membered monocyclic aromaticsystem or a 9-10 membered bicyclic aromatic system containing one ormore heteroatoms selected from nitrogen, oxygen and sulfur, e.g. furan,thiophene, pyrrole, imidazole, pyrazole, triazole, pyridine, pyrazine,pyrimidine, pyridazine, isothiazole, isoxazole, oxazole, oxadiazole,thiadiazole, quinoline, isoquinoline, quinazoline, quinoxaline, indole,benzimidazole, benzofuran, pteridine and purine.

[0211] The term “heteroaryloxy” as used herein, alone or in combination,refers to a heteroaryl as defined herein linked to an oxygen atom havingits free valence bond from the oxygen atom e.g. pyrrole, imidazole,pyrazole, triazole, pyridine, pyrazine, pyrimidine, pyridazine,isothiazole, isoxazole, oxazole, oxadiazole, thiadiazole, quinoline,isoquinoline, quinazoline, quinoxaline, indole, benzimidazole,benzofuran, pteridine and purine linked to oxygen.

[0212] The term “aralkyl” as used herein refers to a straight orbranched saturated carbon chain containing from 1 to 6 carbonssubstituted with an aromatic carbohydride; such as benzyl, phenethyl,3-phenylpropyl, 1-naphtylmethyl, 2-(1-naphtyl)ethyl and the like.

[0213] The term “aryloxy” as used herein refers to phenoxy,1-naphthyloxy or 2-naphthyloxy.

[0214] The term “aralkoxy” as used herein refers to a C₁₋₆-alkoxy groupsubstituted with an aromatic carbohydride, such as benzyloxy,phenethoxy, 3-phenylpropoxy, 1-naphthylmethoxy, 2-(1-naphtyl)ethoxy andthe like.

[0215] The term “heteroaralkyl” as used herein refers to a straight orbranched saturated carbon chain containing from 1 to 6 carbonssubstituted with a heteroaryl group; such as (2-furyl)methyl,(3-furyl)methyl, (2-thienyl)methyl, (3-thienyl)methyl,(2-pyridyl)methyl, 1-methyl-1-(2-pyrimidyl)ethyl and the like.

[0216] The term “heteroaralkoxy” as used herein refers to aheteroaralkyl as defined herein linked to an oxygen atom having its freevalence bond from the oxygen atom, e.g. (2-furyl)methyl,(3-furyl)methyl, (2-thienyl)methyl, (3-thienyl)methyl,(2-pyridyl)methyl, 1-methyl-1-(2-pyrimidyl)ethyl linked to oxygen.

[0217] The term “C₁₋₆-alkylsulfonyl” as used herein refers to amonovalent substituent comprising a C₁₋₆-alkyl group linked through asulfonyl group such as e.g. methylsulfonyl, ethylsulfonyl,n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, sec-butylsulfonyl,isobutylsulfonyl, tert-butylsulfonyl, n-pentylsulfonyl,2-methylbutylsulfonyl, 3-methylbutylsulfonyl, n-hexylsulfonyl,4-methylpentylsulfonyl, neopentylsulfonyl, n-hexylsulfonyl and2,2-dimethylpropylsulfonyl.

[0218] The term “C₁₋₆-monoalkylaminosulfonyl” as used herein refers to amonovalent substituent comprising a C₁₋₆-monoalkylamino group linkedthrough a sulfonyl group such as e.g. methylaminosulfonyl,ethylaminosulfonyl, n-propylaminosulfonyl, isopropylaminosulfonyl,n-butylaminosulfonyl, sec-butylaminosulfonyl, isobutylaminosulfonyl,tert-butylaminosulfonyl, n-pentylaminosulfonyl,2-methylbutylaminosulfonyl, 3-methylbutylaminosulfonyl,n-hexylaminosulfonyl, 4-methylpentylaminosulfonyl,neopentylaminosulfonyl, n-hexylaminosulfonyl and2,2-dimethylpropylaminosulfonyl.

[0219] The term “C₁₋₆-dialkylaminosulfonyl” as used herein refers to amonovalent substituent comprising a C₁₋₆dialkylamino group linkedthrough a sulfonyl group such as dimethylaminosulfonyl,N-ethyl-N-methylaminosulfonyl, diethylaminosulfonyl,dipropylaminosulfonyl, N-(n-butyl)-N-methylaminosulfonyl,di(n-pentyl)aminosulfonyl, and the like.

[0220] The term “C₁₋₆-alkylsulfinyl” as used herein refers to amonovalent substituent comprising a straight or branched C₁₋₆alkyl grouplinked through a sulfinyl group (—S(═O)—); such as e.g. methylsulfinyl,ethylsulfinyl, isopropylsulfinyl, butylsulfinyl, pentylsulfinyl, and thelike.

[0221] The term “acylamino” as used herein refers to an amino groupwherein one of the hydrogen atoms is substituted with an acyl group,such as e.g. acetamido, propionamido, isopropylcarbonylamino, and thelike.

[0222] The term “(C₃₋₆-cycloalkyl)C₁₋₆-alkyl” as used herein, alone orin combination, refers to a straight or branched, saturated hydrocarbonchain having 1 to 6 carbon atoms and being monosubstituted with aC₃₋₆-cycloalkyl group, the cycloalkyl group optionally being mono- orpolysubstituted with C₁₋₆-alkyl, halogen, hydroxy or C₁₋₆-alkoxy; suchas e.g. cyclopropylmethyl, (1-methylcyclopropyl)methyl,1-(cyclopropyl)ethyl, cyclopentylmethyl, cyclohexylmethyl, and the like.

[0223] The term “arylthio” as used herein, alone or in combination,refers to an aryl group linked through a divalent sulfur atom having itsfree valence bond from the sulfur atom, the aryl group optionally beingmono- or polysubstituted with C₁₋₆-alkyl, halogen, hydroxy orC₁₋₆-alkoxy; e.g. phenylthio, (4-methylphenyl)- thio,(2-chlorophenyl)thio, and the like.

[0224] The term “arylsulfinyl” as used herein refers to an aryl grouplinked through a sulfinyl group (—S(═O)—), the aryl group optionallybeing mono- or polysubstituted with C₁₋₆-alkyl, halogen, hydroxy orC₁₋₆-alkoxy; such as e.g. phenylsulfinyl, (4-chlorophenyl)sulfinyl, andthe like.

[0225] The term “arylsulfonyl” as used herein refers to an aryl grouplinked through a sulfonyl group, the aryl group optionally being mono-or polysubstituted with C₁₋₆-alkyl, halogen, hydroxy or C₁₋₆-alkoxy;such as e.g. phenylsulfonyl, tosyl, and the like.

[0226] The term “C₁₋₆-monoalkylaminocarbonyl” as used herein refers to amonovalent substituent comprising a C₁₋₆-monoalkylamino group linkedthrough a carbonyl group such as e.g. methylaminocarbonyl,ethylaminocarbonyl, n-propylaminocarbonyl, isopropylaminocarbonyl,n-butylaminocarbonyl, sec-butylaminocarbonyl, isobutylaminocarbonyl,tert-butylaminocarbonyl, n-pentylaminocarbonyl,2-methylbutaminocarbonyl, 3-methylbutylaminocarbonyl,n-hexylaminocarbonyl, 4-methylpentylaminocarbonyl,neopentylaminocarbonyl, n-hexylaminocarbonyl and2-2-dimethylpropylaminocarbonyl.

[0227] The term “C₁₋₆dialkylaminocarbonyl” as used herein refers to amonovalent substituent comprising a C₁₋₆dialkylamino group linkedthrough a carbonyl group such as dimethylaminocarbonyl,N-ethyl-N-methylaminocarbonyl, diethylaminocarbonyl,dipropylaminocarbonyl, N-(n-butyl)-N-methylaminocarbonyl,di(n-pentyl)aminocarbonyl, and the like.

[0228] The term “₁₋₆C-monoalkylaminocarbonylamino” as used herein refersto an amino group wherein one of the hydrogen atoms is substituted witha C₁₋₆monoalkygaminocarbonyl group, e.g. methylaminocarbonylamino,ethylamino-carbonylamino, n-propylaminocarbonylamino,isopropylaminocarbonylamino, n-butylaminocarbonylamino,sec-butylaminocarbonylamino, isobutylaminocarbonylamino,tert-butylaminocarbonylamino, and 2-methylbutylaminocarbonylamino.

[0229] The term “C₁₋₆-dialkylaminocarbonylamino” as used herein refersto an amino group wherein one of the hydrogen atoms is substituted witha C₁₋₆dialkylaminocarbonyl group, such as di-methylaminocarbonylamino,N-ethyl-N-methylaminocarbonylamino, diethylaminocarbonylamino,dipropylaminocarbonylamino, N-(n-butyl)Nmethylaminocarbonylamino,di(n-pentyl)aminocarbonylamino, and the like.

[0230] As used herein, the phrase “heterocyclyl” means a monovalentsaturated or. unsaturated group being monocyclic and containing one ormore, such as from one to four carbon atom(s), and from one to four N, Oor S atom(s) or a combination thereof. The phrase “heterocyclyl”includes, but is not limited to, 5-membered heterocycles having onehetero atom (e.g. pyrrolidine, pyrroline); 5-membered heterocycleshaving two heteroatoms in 1,2 or 1,3 positions (e.g. pyrazoline,pyrazolidine, 1,2-oxathiolane, imidazolidine, imidazorine, 4-oxazolone);5-membered heterocycles having three heteroatoms (e.g.tetrahydrofurazan); 5-membered heterocycles having four heteroatoms;6-membered heterocycles with one heteroatom (e.g. piperidine);6-membered heterocycles with two heteroatoms (e.g. piperazine,morpholine); 6-membered heterocycles with three heteroatoms; and6-membered heterocycles with four heteroatoms.

[0231] As used herein, the phrase “a divalent heterocyclic group” meansa divalent saturated or unsaturated system being monocyclic andcontaining one or more, such as from one to four carbon atom(s), and oneto four N, O or S atom(s) or a combination thereof. The phrase adivalent heterocyclic group includes, but is not limited to, 5-memberedheterocycles having one hetero atom (e.g. pyrrolidine, pyrroline);5-membered heterocycles having two heteroatoms in 1,2 or 1,3 positions(e.g. pyrazoline, pyrazolidine, 1,2-oxathiolane, imidazolidine,imidazoline, 4-oxazolone); 5-membered heterocycles having threeteteroatoms (e.g. tetrahydrofurazan); 5-membered heterocycles havingfour heteroatoms; 6-membered heterocycles with one heteroatom (e.g.piperidine); 6-membered heterocycles with two heteroatoms (e.g.piperazine, morpholine); 6-membered heterocycles with three heteroatoms;and 6-membered heterocycles with four heteroatoms.

[0232] As used herein, the phrase “a 5-6 membered cyclic ring” means anunsaturated or saturated or aromatic system containing one or morecarbon atoms and optionally from one to four N, O or S atom(s) or acombination thereof. The phrase “a 5-6 membered cyclic ring” includes,but is not limited to, e.g. cyclopentyl, cyclohexyl, phenyl,cyclohexenyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, pyrazolidinyl,pyrazolinyl, piperidyl, piperazinyl, pyrrolyl, 2H-pyrrolyl, imidazolyl,pyrazolyl, triazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl,morpholinyl, thiomorpholinyl, isothiazolyl, isoxazolyl, oxazolyl,oxadiazolyl, thiadiazolyl, 1,3-dioxolanyl, 1,4-dioxolanyl, 5-memberedheterocycles having one hetero atom (e.g. thiophenes, pyrroles, furans);5-membered heterocycles having two heteroatoms in 1,2 or 1,3 positions(e.g. oxazoles, pyrazoles, imidazoles, thiazoles, purines); 5-memberedheterocycles having three heteroatoms (e.g. triazoles, thiadiazoles);5-membered heterocycles having four heteroatoms; 6-membered heterocycleswith one heteroatom (e.g. pyridine, quinoline, isoquinoline,phenanthridine, cyclohepta[b]pyridine); 6-membered heterocycles with twoheteroatoms (e.g. pyridazines, cinnolines, phthalazines, pyrazines,pyrimidines, quinazolines, morpholines); 6-membered heterocycles withthree heteroatoms (e.g. 1, 3, 5-triazine); and 6-membered heterocycleswith four heteroatoms.

[0233] As used herein, the phrase “5- or 6-membered nitrogen containingring” refers to a monovalent substituent comprising a monocyclicunsaturated or saturated or aromatic system containing one or morecarbon, nitrogen, oxygen or sulfur atoms or a combination thereof andhaving 5 or 6 members, e.g. pyrrolidinyl, pyrrolinyl, imidazolidinyl,pyrazolidinyl, pyrazolinyl, piperidyl, piperazinyl, pyrrolyl,2H-pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrazinyl,pyrimidinyl, pyridazinyl, morpholinyl, thiomorpholinyl, isothiazolyl,isoxazolyl, oxazolyl, oxadiazolyl, thiadiazolyl, 1,3-dioxolanyl and1,4-dioxolanyl.

[0234] Certain of the above defined terms may occur more than once inthe above formula (Ia), and upon such occurence each term shall bedefined independently of the other.

[0235] Pharmaceutically acceptable salts forming part of this inventioninclude salts of the carboxylic acid moiety such as alkali metal saltslike Li, Na, and K salts, alkaline earth metal salts like Ca and Mgsalts, salts of organic bases such as lysine, arginine, guanidine,diethanolamine, choline and the like, ammonium or substituted ammoniumsalts, aluminum salts. Salts may include acid addition salts whereappropriate which are, sulphates, nitrates, phosphates, perchlorates,borates, hydrohalides, acetates, tartrates, maleates, citrates,succinates, palmoates, methanesulplionates, benzoates, salicylates,hydroxynaphthoates, benzenesulfonates, ascorbates, glycerophosphates,ketoglutarates and the like. Pharmaceutically acceptable solvates may behydrates or comprising other solvents of crystallization such asalcohols.

[0236] The pharmaceutically acceptable salts are prepared by reactingthe compound of formula (Ia) with 1 to 4 equivalents of a base such assodium hydroxide, sodium methoxide, sodium hydride, potassiumt-butoxide, calcium hydroxide, magnesium hydroxide and the like, insolvents lilke ether, THF, methanol, t-butanol, dioxane, isopropanol,ethanol etc. Mixture of solvents may be used. Organic bases like lysine,arginine, diethanolamine, choline, guandine and their derivatives etc.may also be used. Alternatively, acid addition salts whereeverapplicable are prepared by treatment with acids such as hydrochloricacid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid,p-toluenesulphonic acid, methanesulfonic acid, acetic acid, citric acid,maleic acid salicylic acid, hydroxynaphthoic acid, ascorbic acid,palmitic acid, succinic acid, benzoic acid, benzenesulfonic acid,tartaric acid and the like in solvents like ethyl acetate, ether,alcohols, acetone, THF, dioxane etc. Mixture of solvents may also beused.

[0237] The stereoisomers of the compounds forming part of this inventionmay be prepared by using reactants in their single enantiomeric form inthe process wherever possible or by conducting the reaction in thepresence of reagents or catalysts in their single enantiomer form or byresolving the mixture of stereoisomers by conventional methods. Some ofthe preferred methods include use of microbial resolution, resolving thediastereomeric salts formed with chiral acids such as mandelic acid,camphorsulfonic acid, tartaric acid, lactic acid, and the like whereverapplicable or chiral bases such as brucine, cinchona alkaloids and theirderivatives and the like. Commonly used methods are compiled by Jaqueset al in “Enantiomers, Racemates and Resolution” (Wiley Interscience,1981). More specifically the compound of formula (Ia) may be convertedto a 1:1 mixture of diastereomeric amides by treating with chiralamines, aminoacids, aminoalcohols derived from aminoacids; conventionalreaction conditions may be employed to convert acid into an amide; thediastereomers may be separated either by fractional crystallization orchromatography and the stereoisomers of compound of formula (la) may beprepared by hydrolysing the pure diastereomeric amide.

[0238] Various polymorphs of compound of general formula (Ia) formingpart of this invention may be prepared by crystallization of compound offormula (la) under different conditions. For example, using differentsolvents commonly used or their mixtures for recrystallization;crystallizations at different temperatures; various modes of cooling,ranging from very fast to very slow cooling during crystallizations.Polymorphs may also be obtained by heating or melting the compoundfollowed by gradual or fast cooling. The presence of polymorphs may bedetermined by solid probe nmr spectroscopy, ir spectroscopy,differential scanning calorimetry, powder X-ray diffraction or suchother techniques.

[0239] The invention also relates to a method of preparing the abovementioned compounds.

[0240] A compound of formula (Ia) can be prepared either—when m is equalto 1—as a compound of formula VI, or b)—when m is equal to 0—as acompound of formula XII:

[0241] By alkylating I with a suitable electrophilic reagent to II.(Examples of the electrophilic reagent are: ethylene oxide, ethylbromoacetate followed by reduction of the ester to alcohol,2-bromoethanol and 3-bromopropanol)

[0242] The hydroxy group can be converted to a suitable leaving group(for example to a halogen, sulfonate, phosphor under Mitsunobuconditions) and then reacted with HQ-Ar—R to give III

[0243] When R═CHO, then III can be converted to IV with a Wittig reagent

[0244] Addition to the double bond of suitable reagents give V

[0245] V can either be hydrolysed to the corresponding carboxylic acidor can be reacted further with a suitable reagent to give VI

[0246] The molecule VII mentioned under formation of II can besynthesised in an analogous way starting from HQ-Ar—CHO.

[0247] VII can also be reacted with the proper alkylating reagent togive VIII

[0248] which then can be reacted with I to give VI.

[0249] Yet another way to synthesise the compounds in this invention isto react I with a proper propargyl analogue IX to give X

[0250] X can then be cross coupled with I—Ar—R using a Pd catalyst likePd(PPh₃)₄ or PdCl₂(PPh)₂ to give XI

[0251] If R═CHO the above synthesis sequence (reaction with a Wittigreagent, hydrogenation followed by hydrolysis or derivatisation of thecarboxylic acid) will give the desired product XII

[0252] The compound XIII can also be cross coupled to the propargylderivative IX using a Pd catalyst like Pd(PPh₃)₄ or PdCl₂(PPh)₂ to givethe product XIV

[0253] XIV can then reacted with I to give XI, which can be reactedfurther as described above to give XII.

[0254] L is a leaving group and all other symbols are as definedearlier.

PHARMACOLOGICAL METHODS

[0255] In vitro PPAR alpha and PPAR gamma activation activity.

[0256] Principle

[0257] The PPAR gene transcription activation assays were based ontransient transfection into human HEK293 cells of two plasmids encodinga chimeric test protein and a reporter protein respectively. Thechimeric test protein was a fusion of the DNA binding domain (DBD) fromthe yeast GAL4 transcription factor to the ligand binding domain (LBD)of the human PPAR proteins. The PPAR LBD harbored in addition to theligand binding pocket also the native activation domain (activatingfunction 2=AF2) allowing the fusion protein to function as a PPAR liganddependent transcription factor. The GAL4 DBD will force the fusionprotein to bind only to Gal4 enhancers (of which none existed in HEK293cells). The reporter plasmid contained a Gal4 enhancer driving theexpression of the firefly luciferase protein. After transfection, HEK293cells expressed the GAL4-DBD-PPAR-LBD fusion protein. The fusion proteinwill in turn bind to the Gal4 enhancer controlling the luciferaseexpression, and do nothing in the absence of ligand. Upon addition tothe cells of a PPAR ligand, luciferase protein will be produced inamounts corresponding to the activation of the PPAR protein. The amountof luciferase protein is measured by light emission after addition ofthe appropriate substrate.

[0258] Methods

[0259] Cell culture and transfection: HEK293 cells were grown inDMEM+10% FCS, 1% PS. Cells were seeded in 96-well plates the day beforetransfection to give a confluency of 80% at transfection. 0,8 μg DNA perwell was transfected using FuGene transfection reagent according to themanufacturers instructions (Boehringer-Mannheim). Cells were allowed toexpress protein for 48 h followed by addition of compound.

[0260] Plasmids: Human PPAR α and γ was obtained by PCR amplificationusing cDNA templates from liver, intestine and adipose tissuerespectively. Amplified cDNAs were cloned into pCR2.1 and sequenced. TheLBD from each isoform PPAR was generated by PCR (PPARα: aa 167 - C-term;PPARγ: aa 165 - C-term) and fused to GAL4-DBD by subcloning fragments inframe into the vector pM1 generating the plasmids pM1αLBD and pM1γLBD.Ensuing fusions were verified by sequencing. The reporter wasconstructed by inserting an oligonucleotide encoding five repeats of theGal4 recognition sequence into the pGL2 vector (Promega).

[0261] Compounds: All compounds were dissolved in DMSO and diluted1:1000 upon addition to the cells. Cells were treated with compound(1:1000 in 200 μl growth medium including delipidated serum) for 24 hfollowed by luciferase assay.

[0262] Luciferase assay: Medium including test compound was aspiratedand 100 μl PBS incl. 1 mM Mg⁺⁺ and Ca⁺⁺ was added to each well. Theluciferase assay was performed using the LucLite kit according to, themanufacturers instructions (Packard Instruments). Light emission wasquantified by counting SPC mode on a Packard Instruments top-counter.

PHARMACEUTICAL COMPOSITIONS

[0263] In another aspect, the present invention includes within itsscope pharmaceutical compositions comprising, as an active ingredient,at least one of the compounds of the general formula (Ia) or apharmaceutically acceptable salt thereof together with apharmaceutically acceptable carrier or diluent.

[0264] Pharmaceutical compositions containing a compound of the presentinvention may be prepared by conventional techniques, e.g. as describedin Remington: The Science and Practise of Pharmacy, 19^(th) Ed., 1995.The compositions may appear in conventional forms, for example capsules,tablets, aerosols, solutions, suspensions or topical applications.

[0265] Typical compositions include a compound of formula (Ia) or apharmaceutically acceptable acid addition salt thereof, associated witha pharmaceutically acceptable excipient which may be a carrier or adiluent or be diluted by a carrier, or enclosed within a carrier whichcan be in the form of a capsule, sachet, paper or other container. Inmaking the compositions, conventional techniques for the preparation ofpharmaceutical compositions may be used. For example, the activecompound will usually be mixed with a carrier, or diluted by a carrier,or enclosed within a carrier which may be in the form of a ampoule,capsule, sachet, paper, or other container. When the carrier serves as adiluent, it may be solid, semi-solid, or liquid material which acts as avehicle, excipient, or medium for the active compound. The activecompound can be adsorbed on a granular solid container for example in asachet. Some examples of suitable carriers are water, salt solutions,alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil,peanut oil, olive oil, gelatine, lactose, terra alba, sucrose,cyclodextrin, amylose, magnesium stearate, talc, gelatin, agar, pectin,acacia, stearic acid or lower alkyl ethers of cellulose, silicic acid,fatty acids, fatty acid amines, fatty acid monoglycerides anddiglycerides, pentaerythritol fatty acid esters, polyoxyethylene,hydroxymethylcellulose and polyvinylpyrrolidone. Similarly, the carrieror diluent may include any sustained release material known in the art,such as glyceryl monostearate or glyceryl distearate, alone or mixedwith a wax. The formulations may also include wetting agents,emulsifying and suspending agents, preserving agents, sweetening agentsor flavouring agents. The formulations of the invention may beformulated so as to provide quick, sustained, or delayed release of theactive ingredient after administration to the patient by employingprocedures well known in the art.

[0266] The pharmaceutical compositions can be sterilized and mixed, ifdesired, with auxiliary agents, emulsifiers, salt for influencingosmotic pressure, buffers and/or colouring substances and the like,which do not deleteriously react with the active compounds.

[0267] The route of administration may be any route, which effectivelytransports the active compound to the appropriate or desired site ofaction, such as oral, nasal, pulmonary, transdermal or parenteral e.g.rectal, depot, subcutaneous, intravenous, intraurethral, intramuscular,intranasal, ophthalmic solution or an ointment, the oral route beingpreferred.

[0268] If a solid carrier is used for oral administration, thepreparation may be tabletted, placed in a hard gelatin capsule in powderor pellet form or it can be in the form of a troche or lozenge. If aliquid carrier is used, the preparation may be in the form of a syrup,emulsion, soft gelatin capsule or sterile injectable liquid such as anaqueous or non-aqueous liquid suspension or solution.

[0269] For nasal administration, the preparation may contain a compoundof formula (Ia) dissolved or suspended in a liquid carrier, inparticular an aqueous carrier, for aerosol application. The carrier maycontain additives such as solubilizing agents, e.g. propylene glycol,surfactants, absorption enhancers such as lecithin (phosphatidylcholine)or cyclodextrin, or preservatives such as parabenes.

[0270] For parenteral application, particularly suitable are injectablesolutions or suspensions, preferably aqueous solutions with the activecompound dissolved in polyhydroxylated castor oil.

[0271] Tablets, dragees, or capsules having talc and/or a carbohydratecarrier or binder or the like are particularly suitable for oralapplication. Preferable carriers for tablets, dragees, or capsulesinclude lactose, corn starch, and/or potato starch. A syrup or elixircan be used in cases where a sweetened vehicle can be employed.

[0272] A typical tablet which may be prepared by conventional tablettingtechniques may contain: Core: Active compound (as free compound or saltthereof) 5 mg Colloidal silicon dioxide (Aerosil) 1.5 mg Cellulose,microcryst. (Avicel) 70 mg Modified cellulose gum (Ac-Di-Sol) 7.5 mgMagnesium stearate Ad. Coating: HPMC approx. 9 mg *Mywacett 9-40 Tapprox. 0.9 mg

[0273] The compounds of the invention may be administered to a mammal,especially a human in need of such treatment, prevention, elimination,alleviation or amelioration of diseases related to the regulation ofblood sugar. Such mammals include also animals, both domestic animals,e.g. household pets, and non-domestic animals such as wildlife.

[0274] The compounds of the invention are effective over a wide dosagerange. For example, in the treatment of adult humans, dosages from about0.05 to about 100 mg, preferably from about 0.1 to about 100 mg, per daymay be used. A most preferable dosage is about 0.1 mg to about 70 mg perday. In choosing a regimen for patients it may frequently be necessaryto begin with a dosage of from about 2 to about 70 mg per day and whenthe condition is under control to reduce the dosage as low as from about0.1 to about 10 mg per day. The exact dosage will depend upon the modeof administration, on the therapy desired, form in which administered,the subject to be treated and the body weight of the subject to betreated, and the preference and experience of the physician orveterinarian in charge.

[0275] Generally, the compounds of the present invention are dispensedin unit dosage form comprising from about 0.1 to about 100 mg of activeingredient together with a pharmaceutically acceptable carrier per unitdosage.

[0276] Usually, dosage forms suitable for oral, nasal, pulmonal ortransdermal administration comprise from about 0.001 mg to about 100 mg,preferably from about 0.01 mg to about 50 mg of the compounds of formula(Ia) admixed with a pharmaceutically acceptable carrier or diluent.

[0277] In a further aspect, the present invention relates to a method oftreating and/or preventing type I or type II diabetes.

[0278] In a still further aspect, the present invention relates to theuse of one or more compounds of the general formula (Ia) orpharmaceutically acceptable salts thereof for the preparation of amedicament for the treatment and/or prevention of type I or type IIdiabetes.

[0279] Any novel feature or combination of features described herein isconsidered essential to this invention.

1. A compound of formula (Ia)

wherein ring A fused to the ring containing X and N represents a 5-6membered cyclic ring, optionally substituted with one or more halogen,perhalomethyl, hydroxy, nitro, cyano, formyl, or C₁₋₁₂alkyl,C₄₋₁₂-alkenynyl, C₂₋₁₂-alkenyl, C₂₋₁₂-alkynyl, C₁₋₁₂alkoxy, aryl,aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl,heteroaryloxy, heteroaralkoxy, acyl, acyloxy, hydroxyC₁₋₁₂alkyl, amino,acylamino, C₁₋₁₂alkyl-amino, arylamino, aralkylamino, aminoC₁₋₁₂alkyl,C₁₋₁₂alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl,C₁₋₁₂alkoxyC₁₋₁₂alkyl, aryloxyC₁₋₁₂alkyl, aralkoxyC₁₋₁₂alkyl,C₁₋₁₂alkylthio, thioC₁₋₁₂alkyl, C₁₋₁₂alkoxycarbonylamino,aryloxycarbonylamino, aralkoxycarbonylamino, —COR¹¹, or —SO₂R¹², whereinR¹¹ and R¹² independently of each other are selected from hydroxy,halogen, perhalomethyl, C₁₋₆alkoxy or amino optionally substituted withone or more C₁₋₆alkyl, perhalomethyl or aryl; optionally substitutedwith one or more halogen, perhalomethyl, hydroxy, nitro or cyano; ring Bfused to the ring containing X and N represents a 5-6 membered cyclicring, optionally substituted with one or more halogen, perhalomethyl,hydroxy, nitro, cyano, formyl, or C₁₋₁₂alkyl, C₄₋₁₂-alkenynyl,C₂₋₁₂-alkenyl, C₂₋₁₂-alkynyl, C₁₋₁₂alkoxy, aryl, aryloxy, aralkyl,aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy,heteroaralkoxy, acyl, acyloxy, hydroxyC₁₋₁₂alkyl, amino, acylamino,C₁₋₁₂alkyl-amino, arylamino, aralkylamino, aminoC₁₋₁₂alkyl,C₁₋₁₂alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl,C₁₋₁₂alkoxyC₁₋₁₂alkyl, aryloxyC₁₋₁₂alkyl, aralkoxyC₁₋₁₂alkyl,C₁₋₁₂alkylthio, thioC₁₋₁₂alkyl, C₁₋₁₂alkoxycarbonylamino,aryloxycarbonylamino, aralkoxycarbonylamino, —COR¹¹, or —SO₂R¹²,wherein, R¹¹ and R¹² independently of each other are selected fromhydroxy, halogen, perhalomethyl, C₁₋₆alkoxy or amino optionallysubstituted with one or more C₁₋₆alkyl, perhalomethyl or aryl;optionally substituted with one or more halogen, perhalomethyl, hydroxy,nitro or cyano; X is a valence bond, —(CHR⁹)—, —(CHR⁹)—CH₂—, —CH═CH',—O—, —O—(CHR⁹)—, —S—(CHR⁹)—, —(NR⁹)—CH₂—, —(CHR⁹)—CH═CH—,—(CHR⁹)—CH₂—CH₂—, —(C═O)—, —O—CH₂—O—, —(NR⁹)—, —(NR⁹)—S(O₂)—,—CH═(CR⁹)—, —(CO)—(CHR⁹)—, —CH₂—(SO)—, —S—, —(SO)—, —(SO₂)—,—CH₂—(SO₂)—, —CH₂—O—CH₂—, wherein R⁹ is hydrogen, halogen, hydroxy,nitro, cyano, formyl, C₁₋₁₂alkyl, C₁₋₁₂alkoxy, aryl, aryloxy, aralkyl,aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy,heteroaralkoxy, acyl, acyloxy, hydroxyalkyl, amino, acylamino,C₁₋₁₂alkyl-amino, arylamino, aralkylamino, aminoC₁₋₁₂alkyl,C₁₋₁₂alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl,C₁₋₁₂alkoxyC₁₋₁₂alkyl, aryloxyC₁₋₁₂alkyl, aralkoxyC₁₋₁₂alkyl,C₁₋₁₂alkylthio, thioC₁₋₁₂alkyl, C₁₋₁₂alkoxycarbonylamino,aryloxycarbonylamino, aralkoxycarbonylamino, —COR¹¹, or —SO₂R¹², whereinR¹¹ and R¹² independently of each other are selected from hydroxy,halogen, C₁₋₆alkoxy, amino optionally substituted with one or moreC₁₋₆alkyl, perhalomnethyl or aryl; Q is —O—, —S—, >SO₂, >NR¹³, whereinR¹³ is hydrogen or C₁₋₆alkyl, Ar represents arylene, heteroarylene, or adivalent heterocyclic group optionally substituted with one or moreC₁₋₆alkyl or aryl; R⁵ represents hydrogen, hydroxy, halogen,C₁₋₁₂alkoxy, C₁₋₁₂alkyl, C₄₋₁₂-alkenynyl, C₂₋₁₂-alkenyl, C₂₋₁₂-alkynylor aralkyl; optionally substituted with one or more halogen,perhalomethyl, hydroxy, nitro or cyano; or R⁵ forms a bond together withR⁶, R⁶ represents hydrogen, hydroxy, halogen, C₁₋₁₂alkoxy, C₁₋₁₂alkyl,C₄₋₁₂-alkenynyl, C₂₋₁₂-alkenyl, C₂₋₁₂-alkynyl, acyl or aralkyl;optionally substituted with one or more halogen, perhalomethyl, hydroxy,nitro or cyano; or R⁶ forms a bond together with R⁵, R⁷ representshydrogen, C₁₋₁₂alkyl, C₁₋₁₂-alkenynyl, C₂₋₁₂-alkenyl, C₂₋₁₂-alkynyl,aryl, aralkyl, C₁₋₁₂alkoxyC₁₋₁₂alkyl, C₁₋₁₂alkoxycarbonyl,aryloxycarbonyl, C₁₋₁₂alkylaminocarbonyl, arylamino-carbonyl, acyl,heterocyclyl, heteroaryl or heteroaralkyl groups; optionally substitutedwith one or more halogen, perhalomethyl, hydroxy, nitro or cyano; R⁸represents hydrogen, C₁₋₁₂alkyl, C₄₋₁₂-alkenynyl, C₂₋₁₂-alkenyl,C₂₋₁₂-alkynyl, aryl, aralkyl, heterocyclyl, heteroaryl or heteroaralkylgroups; optionally substituted with one or more halogen, perhalomethyl,hydroxy, nitro or cyano; Y represents oxygen, sulphur or NR¹⁰, where R¹⁰represents hydrogen, C₁₋₁₂alkyl, aryl, hydroxyC₁₋₁₂alkyl or aralkylgroups or when Y is NR¹⁰, R⁸ and R¹⁰ may form a 5 or 6 membered nitrogencontaining ring, optionally substituted with one or more C₁₋₆alkyl; n isan integer ranging from 1 to 4 and m is an integer ranging from 0 to 1,provided that A or B does not represent phenyl; or a pharmaceuticallyacceptable salt thereof.
 2. A compound according to claim 1 wherein ringA fused to the ring containing X and N represents a 5-6 membered cyclicring, optionally substituted with one or more hydrogen, halogen,perhalomethyl, hydroxy, cyano, or C₁₋₇alkyl, C₄₋₇-alkenynyl,C₂₋₇-alkenyl, C₂₋₇-alkynyl, C₁₋₇alkoxy, aryl, aryloxy, aralkyl,aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy,heteroaralkoxy, acyl, acyloxy, hydroxyC₁₋₇alkyl, amino, acylamino,C₁₋₇alkyl-amino, arylamino, aralkylamino, aminoC₁₋₇alkyl,C₁₋₇alkoxyC₁₋₇alkyl, aryloxyC₁₋₇alkyl, aralkoxyC₁₋₇alkyl,C₁₋₇,alkylthio, thioC₁₋₇alkyl, C₁₋₇alkoxycarbonylamino,aryloxycarbonylamino, aralkoxycarbonylamino, —COR¹¹, or —SO₂R¹², whereinR¹¹ and R¹² independently of each other are selected from hydroxy,perhalomethyl or amino optionally substituted with one or moreC₁₋₆alkyl, perhalomethyl or aryl; optionally substituted with one ormore halogen, perhalomethyl, hydroxy or cyano.
 3. A compound accordingto anyone of the preceding claims wherein ring A fused to the ringcontaining X and N represents a 5-6 membered cyclic ring, optionallysubstituted with one or more hydrogen, halogen, perhalomethyl, hydroxy,cyano, or C₁₋₇alkyl, C₄₋₇-alkenynyl, C₂₋₇-alkenyl, C₂₋₇-alkynyl,C₁₋₇alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl,heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, amino, acylamino,C₁₋₇alkyl-amino, arylamino, aralkylamino, aminoC₁₋₇alkyl,C₁₋₇alkoxyC₁₋₇alkyl, aryloxyC₁₋₇alkyl, aralkoxyC₁₋₇alkyl, C₁₋₇alkylthio,thioC₁₋₇alkyl; optionally substituted with one or more halogen orhydroxy;
 4. A compound according to anyone of the preceding claimswherein ring A fused to the ring containing X and N represents a 5-6membered cyclic ring, optionally substituted with one or more hydrogen,halogen, perhalomethyl, hydroxy or C₁₋₇alkyl, C₂₋₇-alkenyl,C₂₋₇-alkynyl, C₁₋₇alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl,heteroaryloxy, heteroaralkoxy, acyl, arylamino, aryloxyC₁₋₇alkyl.
 5. Acompound according to anyone of the preceding claims wherein ring Afused to the ring containing X and N represents a 5-6 membered cyclicring, optionally substituted with one or more hydrogen, halogen,perhalomethyl, hydroxy or C₁₋₇alkyl, C₂₋₇alkenyl, C₂₋₇-alkynyl,C₁₋₇alkoxy or aryl.
 6. A compound according to anyone of the precedingclaims wherein ring A fused to the ring containing X and N represents a5-6 membered cyclic ring, optionally substituted with one or morehydrogen or halogen.
 7. A compound according to anyone of the precedingclaims wherein ring B fused to the ring containing X and N represents a5-6 membered cyclic ring, optionally substituted with one or morehydrogen, halogen, perhalomethyl, hydroxy, cyano, or C₁₋₇alkyl,C₄₋₇alkenynyl, C₂₋₇-alkenyl, C₂₋₇-alkynyl, C₁₋₇alkoxy, aryl, aryloxy,aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl,heteroaryloxy, heteroaralkoxy, acyl, acyloxy, hydroxyC₁₋₇alkyl, amino,acylamino, C₁₋₇alkyl-amino, arylamino, aralkylamino, aminoC₁₋₇alkyl,C₁₋₇alkoxyC₁₋₇alkyl, aryloxyC₁₋₇alkyl, aralkoxyC₁₋₇alkyl, C₁₋₇alkylthio,thioC₁₋₇alkyl, C₁₋₇alkoxycarbonylamino, aryloxycarbonylamino,aralkoxycarbonylamino, —COR¹¹, or —SO₂R¹², wherein R¹¹ and R¹²independently of each other are selected from hydroxy, perhalomethyl oramino optionally substituted with one or more C₁₋₆alkyl, perhalomethylor aryl; optionally substituted with one or more halogen, perhalomethyl,hydroxy or cyano.
 8. A compound according to anyone of the precedingclaims wherein ring B fused to the ring containing X and N represents a5-6 membered cyclic ring, optionally substituted with one or morehydrogen, halogen, perhalomethyl, hydroxy, cyano, or C₁₋₇alkyl,C₄₋₇alkenynyl, C₂₋₇-alkenyl, C₂₋₇-alkynyl, C₁₋₇alkoxy, aryl, aryloxy,aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl,heteroaryloxy, heteroaralkoxy, acyl, amino, acylamino, C₁₋₇alkyl-amino,arylamino, aralkylamino, aminoC₁₋₇alkyl, C₁₋₇alkoxyC₁₋₇alkyl,aryloxyC₁₋₇alkyl, aralkoxyC₁₋₇alkyl, C₁₋₇alkylthio, thioC₁₋₇alkyl;optionally substituted with one or more halogen or hydroxy.
 9. Acompound according to anyone of the preceding claims wherein ring Bfused to the ring containing X and N represents a 5-6 membered cyclicring, optionally substituted with one or more hydrogen, halogen,perhalomethyl, hydroxy or C₁₋₇alkyl, C₂₋₇alkenyl, C₂₋₇-alkynyl,C₁₋₇alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heteroaryl, heteroaryloxy,heteroaralkoxy, acyl, arylamino, aryloxyC₁₋₇alkyl.
 10. A compoundaccording to anyone of the preceding claims wherein ring B fused to thering containing X and N represents a 5-6 membered cyclic ring,optionally substituted with one or more hydrogen, halogen,perhalomethyl, hydroxy or C₁₋₇alkyl, C₂₋₇alkenyl,C₂₋₇-alkynyl,C₁₋₇alkoxy or aryl.
 11. A compound according to anyone ofthe preceding claims wherein ring B fused to the ring containing X and Nrepresents a 5-6 membered cyclic ring, optionally substituted with oneor more hydrogen or halogen.
 12. A compound according to anyone of thepreceding claims wherein X is a valence bond, —(CHR⁹)—, —(CHR⁹)—CH₂—,—CH═CH—, —O—, —O—(CHR⁹)—, —S—(CHR⁹)—, —(NR⁹)—CH₂—, —(CHR⁹)—CH═CH—,—(CHR⁹)—CH₂—CH₂—, —(C═O)—, —O—CH₂—O—, —(NR⁹)—, —(NR⁹)—S(O₂)—,—CH═(CR⁹)—, —(CO)—(CHR⁹)—, —CH₂—(SO)—, —S—, —(SO)—, —(SO₂)—,—CH₂—(SO₂)—, —CH₂—O—CH₂—, wherein R⁹ is hydrogen, halogen, hydroxy,cyano, C₁₋₇alkyl, C₁₋₇alkoxy, aryl, aryloxy, aralkyl, aralkoxy,heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy,acyl, acyloxy, hydroxyalkyl, amino, acylamino, C₁₋₇alkyl-amino,arylamino, aralkylamino, aminoC₁₋₇alkyl, C₁₋₇alkoxyC₁₋₇alkyl,aryloxyC₁₋₇alkyl, aralkoxyC₁₋₇alkyl, C₁₋₇alkylthio, thioC₁₋₇alkyl.
 13. Acompound according to anyone of the preceding claims wherein X is avalence bond, —(CHR⁹)—, —(CHR⁹)—CH₂—, —CH═CH—, —O—, —O—(CHR⁹)—,—S—(CHR⁹)—, —(NR⁹)—CH₂—, —(CHR⁹)—CH═CH—, —(CHR⁹)—CH₂—CH₂—, —(C═O)—,—O—CH₂—O—, —(NR⁹)—, —(NR⁹)—S(O₂)—, —CH═(CR⁹)—, —(CO)—(CHR⁹)—,—CH₂—(SO)—, —S—, —(SO)—, —(SO₂)—, —CH₂—(SO₂)—, —CH₂—O—CH₂—, wherein R⁹is hydrogen, halogen, hydroxy, C₁₋₇alkyl, C₁₋₇alkoxy, aryl.
 14. Acompound according to anyone of the preceding claims wherein X is avalence bond, —(CHR⁹)—, —(CHR⁹)—CH₂—, —CH═CH—, —O—(CHR⁹)—, —S—(CHR⁹)—,—(NR⁹)—CH₂—, —(CHR⁹)—CH═CH—, —(CHR⁹)—CH₂—CH₂—, —(C═O)—, —O—CH₂—O—,—(NR⁹)—S(O₂)—, —CH═(CR⁹)—, —(CO)—(CHR⁹)—, —CH₂—(SO)—, —(SO)—, —(SO2)—,—CH₂—(SO₂)—, —CH₂—O—CH₂— wherein R⁹ is hydrogen, halogen, hydroxy,C₁₋₄alkyl, C₁₋₄alkoxy.
 15. A compound according to anyone of thepreceding claims wherein X is a valence bond, —(CHR⁹)—, —(CHR⁹)—CH₂—,—CH═CH—, —O—(CHR⁹)—, —(CHR⁹)—CH═CH—, —(CHR⁹)—CH₂—CH₂—, —(C═O)—,—O—CH₂—O—, —CH═(CR⁹)—, —(CO)—(CHR⁹)—, —CH₂—(SO)—, —(SO)—, —(SO₂)—,—CH₂—(SO₂)—, —CH₂—O—CH₂—, wherein R⁹ is hydrogen.
 16. A compoundaccording to anyone of the preceding claims wherein Q is —O— or —S—. 17.A compound according to anyone of the preceding claims wherein Q is —O—.18. A compound according to anyone of the preceding claims wherein Arrepresents arylene, heteroarylene, or a divalent heterocyclic groupoptionally substituted with one or more C₁₋₆alkyl or aryl; R⁵ representshydrogen, hydroxy, halogen, C₁₋₇alkoxy, C₁₋₇alkyl, C₄₋₇-alkenynyl,C₂₋₇-alkenyl, C₂₋₇-; or R⁵ forms a bond together with R⁶, R⁶ representshydrogen, hydroxy, halogen, C₁₋₇alkoxy, C₁₋₇alkyl, C₄₋₇alkenynyl,C₂₋₇-alkenyl, C₂₋₇-alkynyl; or R⁶ forms a bond together with R⁵, R⁷represents hydrogen, C₁₋₇alkyl, C₄₋₇alkenynyl, C₂₋₇-alkenyl,C₂₋₇-alkynyl, aryl, aralkyl, C₁₋₇alkoxyC₁₋₇alkyl, C₁₋₇alkoxycarbonyl,aryloxycarbonyl, C₁₋₇alkylaminocarbonyl, arylaminocarbonyl, acyl,heterocyclyl, heteroaryl or heteroaralkyl groups; R⁸ representshydrogen, C₁₋₇alkyl, C₄₋₇-alkenynyl, C₂₋₇-alkenyl, C₂₋₇-alkynyl, aryl,aralkyl, heterocyclyl, heteroaryl or heteroaralkyl; Y represents oxygen,sulphur or NR¹⁰ , where R¹⁰ represents hydrogen, C₁₋₇alkyl,hydroxyC₁₋₇alkyl; n is an integer ranging from 2 to 3 and m is aninteger ranging from 0 to
 1. 19. A compound according to anyone of thepreceding claims wherein Ar represents arylene or heteroarylene, R⁵represents hydrogen, hydroxy, halogen; or R⁵ forms a bond together withR⁶, R⁶ represents hydrogen, hydroxy, halogen; or R⁶ forms a bondtogether with R⁵, R⁷ represents hydrogen, C₁₋₇alkyl, C₂₋₇-alkenyl,C₂₋₇-alkynyl, aryl, aralkyl, C₁₋₇alkoxyC₁₋₇alkyl,C₁₋₇alkylaminocarbonyl, arylaminocarbonyl, acyl, heterocyclyl,heteroaryl or heteroaralkyl groups; R⁸ represents hydrogen, C₁₋₇alkyl,C₂₋₇-alkenyl, C₂₋₇-alkynyl,; Y represents oxygen or sulphur; n is aninteger ranging from 2 to 3 and m is
 1. 20. A compound according toanyone of the preceding claims wherein Ar represents arylene orheteroarylene; R⁵ represents hydrogen; R⁶ represents hydrogen; R⁷represents hydrogen, C₁₋₇alkyl, C₂₋₇-alkenyl, C₂₋₇-alkynyl, aryl,aralkyl, C₁₋₇alkoxyC₁₋₇alkyl; R⁸ represents hydrogen, C₁₋₇alkyl,C₂₋₇-alkenyl, C₂₋₇alkynyl,; Y represents oxygen; n is an integer rangingfrom 2 to 3 and m is
 1. 21. A compound according to anyone of thepreceding claims wherein Ar represents arylene R⁵ represents hydrogen;R⁸ represents hydrogen; R⁷ represents hydrogen, C₁₋₄alkyl, C₂₋₄-alkenyl,C₂₋₄-alkynyl, R⁸ represents hydrogen, C₁₋₄alkyl, Y represents oxygen; nis an integer ranging from 2 to 3 and m is
 1. 22. A compound accordingto anyone of the preceding claims wherein Ar represents phenylene, R⁵represents hydrogen; R⁶ represents hydrogen; R⁷ represents hydrogen,C₁₋₄alkyl, R⁸ represents hydrogen Y represents oxygen; n is an integerranging from 2 to 3 and m is
 1. 23. A compound according to anyone ofthe preceding claims wherein A is 5 membered cyclic ring containing S.24. A compound according to anyone of the preceding claims wherein B is5 membered cyclic ring containing S.
 25. A compound according to anyoneof the preceding claims wherein X is —CH═(CR⁹)—, wherein R⁹ is H.
 26. Acompound according to anyone of the preceding claims wherein n is
 2. 27.A compound according to anyone of the preceding claims wherein Q is —O—.28. A compound according to anyone of the preceding claims wherein m is1.
 29. A compound according to anyone of the preceding claims wherein Aris phenylene. In another preferred embodiment, the present invention isconcerned with compounds of formula I wherein R⁵ is H.
 30. A compoundaccording to anyone of the preceding claims wherein R⁶ is H.
 31. Acompound according to anyone of the preceding claims wherein R⁷ isethyl.
 32. A compound according to anyone of the preceding claimswherein Y is oxygen.
 33. A compound according to anyone of the precedingclaims wherein R⁸ is H.
 34. The compound according to claim 1 which is:3-{4-[2(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)ethoxy]-phenyl}-2-ethoxy-propionicacid,3-{4-[2-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen4-yl)ethoxy]-phenyl}-2-methoxy-propionicacid,3-{4-[2-(8,9-Dihydro-3,5-dithia4-aza-cyclopenta[f]azulen-4-yl)ethoxy]-phenyl}-2-propoxy-propionicacid,3-{4-[2-(8,9-Dihydro-3,5-dithia4-aza-cyclopenta[f]azulen-4-yl)ethoxy]-phenyl}-2-benzyloxy-propionicacid,3-{4-[2-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)ethyl]-phenyl}-2-ethoxy-propionicacid,3-{4-[2-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)ethyl]-phenyl}-2-methoxy-propionicacid,3-{4-[2-(8,9-Dihydro-3,5-dithia4-aza-cyclopenta[f]azulen-4-yl)ethyl]-phenyl}-2-propoxy-propionicacid,3-{4-[2-(8,9-Dihydro-3,5-dithia4-aza-cyclopenta[f]azulen-4-yl)ethyl]-phenyl}-2-benzyloxy-propionicacid,3-{4-[1-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)methoxy]-phenyl}-2-ethoxy-propionicacid,3-{4-[1-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)methoxy]-phenyl}-2-methoxy-propionicacid,3-{4-[1-(8,9-Dihydro-3,5-dithia4-aza-cyclopenta[f]azulen-4-yl)methoxy]-phenyl}-2-benzyloxy-propionicacid,3-{4-[3-(8,9-Dihydro-3,5dithia4-aza-cyclopenta[f]azulen-4-yl)propoxy]-phenyl}-2-ethoxy-propionicacid,3-{4-[3-(8,9-Dihydra-3,5-dithia-4-aza-cyclopenta[f]azulen-4yl)propoxy]-phenyl}-2-methoxy-propionicacid,3-{4-[3-(8,9-Dihydro-3,5-dithia-4-aza-cyclopenta[f]azulen-4-yl)propoxy]-phenyl}-2-benzyloxy-propionicacid,3-{4-[3-(8,9-Dihydro-3,5dithia4-aza-cyclopenta[f]azulen-4-yl)propyl]-phenyl}-2-ethoxy-propionicacid,3-{4-[3-(8,9-Dihydro-3,5-dithia4-aza-cyclopenta[f]azulen-4-yl)propyl]-phenyl}-2-methoxy-propionicacid,3-{4-[3-(8,9-Dihydro-3,5dithia-4-aza-cyclopenta[f]azulen-4-yl)propyl]-phenyl}-2-benzyloxy-propionicacid, 2-Ethoxy-3(4-(2(9H-1, 8,10-triaza-anthracen-10-yl)ethoxy)phenyl)propionic acid,2-methoxy-3(4-(2(9H-1, 8,10-triaza-anthracen-10-yl)ethoxy)phenyl)propionic acid,2-propoxy-3-(4-(2-(9H-1, 8,10-triaza-anthracen-10-yl)ethoxy)phenyl)propionic acid,2-benzyloxy-3-(4-(2-(9H-1,8,10-triaza-anthracen-10-yl)ethoxy)phenyl)propionic acid,2-ethoxy-3-(4-(1-(9H-1 ,8,10-triaza-anthracen-10-yl)methoxy)phenyl)propionic acid,2-methoxy-3-(4-(1-(9H-1, 8,10-triaza-anthracen-10-yl)methoxy)phenyl)propionic acid,2-benzyloxy-3-(4-(1-(9H-1, 8,10-triaza-anthracen-10-yl)methoxy)phenyl)propionic acid,2-ethoxy-3-(4-(3-(9H-1 ,8,10-triaza-anthracen-10-yl)propoxy)phenyl)propionic acid,2-propoxy-3-(4-(3-(9H-1, 8,10-triaza-anthracen-10-yl)propoxy)phenyl)propionic acid,2-methoxy-3-(4-(3-(9H-1, 8,10-triaza-anthracen-10-yl)propoxy)phenyl)propionic acid,2-benzyloxy-3-(4-(3-(9H-1, 8,10-triaza-anthracen-10-yl)propoxy)phenyl)propionic acid,2-ethoxy-3-(4-(3-(9H-1, 8,10-triaza-anthracen-10-yl)propyl)phenyl)propionic acid,2-propoxy-3-(4-(3-(9H-1,8,10-triaza-anthracen-10-yl)propyl)phenyl)propionic acid,2-methoxy-3-(4-(3-(9H-1, 8,10-triaza-anthracen-10-yl)propyl)phenyl)propionic acid,2-benzyloxy-3-(4-(3-(9H-1, 8,10-triaza-anthracen-10-yl)propyl)phenyl)propionic acid,2-deoxy-3-(4-(3-(4, 5, 9H -triaza- anthracen-10-yl)propyl)proprin acid,2-methoxy-3-(4-(2-(4, 5, 9-triaza-fluoren-9-yl)ethoxy)phenyl)propionicacid, 2-propoxy-3-(⁴-(2-(4, 5,9-triaza-fluoren-9-yl)ethoxy)phenyl)propionic acid, 2-ethoxy-3-(4-(1-(4,5, 9-triaza-fluoren-9-yl)methoxy)phenyl)propionic acid,2-methoxy-3-(4-(1-(4, 5, 9-triaza-fluoren-9-yl)methoxy)phenyl)propionicacid, 2-benzyloxy-3-(4-(1-(4, 5,9-triaza-fluoren-9-yl)methoxy)phenyl)-propionic acid,2-ethoxy-3-(4-(3-(4, 5, 9-triaza-fluoren-9-yl)propoxy)phenyl)propionicacid, 2-methoxy-3-(4-(1-(4, 5,9-triaza-fluoren-9-yl)methoxy)phenyl)propionic acid,2-benzyloxy-3-(4-(1-(4, 5,9-triaza-fluoren-9-yl)methoxy)phenyl)propionic acid,2-propoxy-3-(4-(3-(4, 5, 9-triaza-fluoren-9-yl)propoxy)phenyl)propionicacid, 2-ethoxy-3-(4-(3-(4, 5,9-triaza-fluoren-9-yl)propyl)phenyl)propionic acid, 2-ethoxy-3-(4-(3-(4,5, 9-triaza-fluoren-9-yl)propyl)phenyl)propionic acid,2-benzyloxy-3-(4-(3-(4, 5, 9-triaza-fluoren-9-yl)propyl)phenyl)propionicacid, 2-propoxy-3-(4-(3-(4, 5,9-triaza-fluoren-9-yl)propyl)phenyl)propionic acid, 2-ethoxy-3-(4-(2-(4,8, 9-triaza-fluoren-9-yl)ethoxy)phenyl)propionic acid,2-ethoxy-3-(4-(2-(1, 8, 9-triaza-fluoren-9-yl)ethoxy)phenyl)propionicacid, 2-propoxy-3-(4-(2-(1, 8,9-triaza-fluoren-9-yl)ethoxy)phenyl)propionic acid,2-benzyoxy-3-(4-(2-(1, 8, 9-triaza-fluoren-9-yl)ethoxy)phenyl)propionicacid, 2-methoxy-3-(4-(1-(1, 8,9-triaza-fluoren-9-yl)methoxy)phenyl)propionic acid,2-ethoxy-3-(4-(1-(1, 8, 9-triaza-fluoren-9-yl)methoxy)phenyl)propionicacid, 2-propoxy-3-(4-(1-(1, 8,9-triaza-fluoren-9-yl)methoxy)phenyl)propionic acid,2-benzyloxy-3-(4-(1-(1, 8,9-triaza-fluoren-9-yl)methoxy)phenyl)propionic acid,2-ethoxy-3-(4-(3-(1, 8, 9-triaza-fluoren-9-yl)propoxy)phenyl)propionicacid, 2-methoxy-3-(4-(3-(1, 8,9-triaza-fluoren-9-yl)propoxy)phenyl)propionic acid,2-propoxy-3-(4-(3-(1, 8, 9-triaza-fluoren-9-yl)propoxy)phenyl)propionicacid, 2-benzyloxy-3-(4(3-(1, 8,9-triaza-fluoren-9-yl)propoxy)phenyl)propionic acid,2-ethoxy-3-(4-(3-(1, 8, 9-triaza-fluoren-9-yl)propyl)phenyl)propionicacid, 2-methoxy-3-(4-(3-(1, 8,9-triaza-fluoren-9-yl)propyl)phenyl)propionic acid,2-propoxy-3-(4-(3-(1, 8, 9-triaza-fluoren-9-yl)propyl)phenyl)propionicacid, 2-benzyloxy-3-(4-(3-(1, 8,9-triaza-fluoren-9-yl)propyl)phenyl)propionic acid,3-(4-(2-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)ethoxy)phenyl)2-ethoxy-propionic acid,3-(4-(2-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)ethoxy)phenyl)2-methoxy-propionic acid,3-(4-(2-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)ethoxy)phenyl)2-propoxy-propionic acid,3-(4-(2-(dithieno[2, 3-b;3′,2′-d]pyrrol-7-yl)ethoxy)phenyl)2-benzyloxy-propionic acid,3-(4-(1-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)methoxy)phenyl)2-methoxy-propionic acid,3-(4-(1-(dithieno[2,3-b; 3′,2′-d]pyrrol-7-yl)methoxy)phenyl)2-ethoxy-propionic acid,3-(4-(1-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)methoxy)phenyl)2-proxy-propionic acid,3-(4-(1-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)methoxy)phenyl)2-propoxy-propionic acid,3-(4-(1-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)methoxy)phenyl)2-benzyloxy-propionic acid,3-(4-(3-(dithienol2,3-b;3′,2′-d]pyrrol-7-yl)propoxy)phenyl)2-methoxy-propionic acid,3-(4-(3-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)propoxy)phenyl)2-ethoxy-propionic acid,3-(4-(3-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)propoxy)phenyl)2-benzoxy-propionic acid,3-(4-(3-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)propoxy)phenyl)2-ethoxy-propionic acid,3-(4-(3-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)propy)phenyl)2-methoxy-propionic acid,3-(4-(3-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)propyl)phenyl)2-ethoxy-propionic acid,3-(4-(3-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)propyl)phenyl)2-benzoxy-propionic acid,3-(4-(3-(dithieno[2,3-b;3′,2′-d]pyrrol-7-yl)propyl)phenyl)2-ethoxy-propionic acid,3-(4-(2-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)ethoxy)phenyl)2-methoxy-propionic acid,3-(4-(2-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)ethoxy)phenyl)2-ethoxy-propionic acid,3-(4-(2-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)ethoxy)phenyl)2-benzoxy-propionic acid,3-(4-(1-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)ethoxy)phenyl)2-ethoxy-propionic acid,3-(4-(1-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)methoxy)phenyl)2-ethoxy-prop ionic acid,3-(4-(1-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)methoxy)phenyl)2-propoxy-propionic acid,3-(4-(1-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)methoxy)phenyl)2-benzyloxy-propionic acid,3-(4-(3-(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)propoxy)phenyl)2-ethoxy-propionic acid,3-(4-(3(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)propoxy)phenyl)2-propoxy-propionic acid,3-(4-(3(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)propoxy)phenyl)2-methoxy-propionic acid,3-(4-(3(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)propoxy)phenyl)2-benzyloxy-propionic acid,3-(4-(3(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)propyl)phenyl)2-ethoxy-propionic acid,3-(4-(3(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)propyl)phenyl)2-propoxy-propionic acid,3-(4-(3(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)propyl)phenyl)2-methoxy-propionic acid,3-(4-(3(difurano[2,3-b;3′,2′-d]pyrrol-7-yl)propyl)phenyl)2-benzyloxy-propionic acid,3-(4-(2(4H-1,7-dithia-8-aza-s-indacen-8-yl)ethoxy)phenyl)2-ethoxy-propionicacid,3-(4-(2(4H-1,7-dithia-8-aza-s-indacen-8-yl)ethoxy)phenyl)2-methoxy-propionicacid,3-(4-(2(4H-1,7-dithia-8-aza-s-indacen-8-yl)ethoxy)phenyl)2-propoxy-propionicacid,3-(4-(2(4H-1,7-dithia-8-aza-s-indacen-8-yl)ethoxy)phenyl)1-2-benzyloxy-propionicacid,3-(4-(1(4H-1,7-dithia-8-aza-s-indacen-8-yl)methoxy)phenyl)2-ethoxy-propionicacid,3-(4-(1(4H-1,7-dithia-8-aza-s-indacen-8-yl)methoxy)phenyl)2-methoxy-propionicacid,3-(4-(1(4H-1,7-dithia-8-aza-s-indacen-8-yl)methoxy)phenyl)1-2-propoxy-propionicacid,3-(4-(1(4H-1,7-dithia-8-aza-s-indacen-8-yl)methoxy)phenyl)2-benzyloxy-propionicacid,3-(4-(3(4H-1,7-dithia-8-aza-s-indacen-8-yl)propoxy)phenyl)2-ethoxy-propionicacid,3-(4-(3(4H-1,7-dithia-8-aza-s-indacen-8-yl)propoxy)phenyl)2-methoxy-propionicacid,3-(4-(3(4H-1,7-dithia-8-aza-s-indacen-8-yl)propoxy)phenyl)2-propoxy-propionicacid,3-(4-(3(4H-1,7-dithia-8-aza-s-indacen-8-yl)propoxy)phenyl)2-benzyloxy-propionicacid,3-(4-(3(4H-1,7-dithia-8-aza-s-indacen-8-yl)propyl)phenyl)2-ethoxy-propionicacid,3-(4-(3(4H-1,7-dithia-8-aza-s-indacen-8-yl)propyl)phenyl)2-methoxy-propionicacid,3-(4-(3(4H-1,7-dithia-8-aza-s-indacen-8-yl)propyl)phenyl)2-propoxy-propionicacid, 3-(4-(3(4H-1,7-dithia-8-aza-s-indacen-8-yl)propyl)phenyl)2-benzoxy-propionicacid, 2-ethoxy-3-(4-(2(4-oxa-1,8-aza-s-indacen-8-yl)ethoxy)phenyl)-propionic acid,2-ethoxy-3-(4-(2(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)ethoxy)phenyl)propionicacid,2-propoxy-3-(4-(2(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)ethoxy)phenyl)propionicacid,2-propoxy-3-(4-(2(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)ethoxy)phenyl)propionicacid,2-benzyloxy-3-(4-(2(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)ethoxy)phenyl)propionicacid,2-ethoxy-3-(4-(1-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)methoxy)phenyl)propionicacid,2-methoxy-3-(4-(1-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)methoxy)phenyl)propionicacid, 32-propoxy-3-(4-(1-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)methoxy)phenyl)propionicacid,2-benzyloxy-3-(4-(1-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)methoxy)phenyl)propionicacid,2-ethoxy-3-(4-(3-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)propoxy)phenyl)propionicacid,2-methoxy-3-(4-(3-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)propoxy)phenyl)propionicacid,2-propoxy-3-(4-(3-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)propoxy)phenyl)propionicacid,2-benzyloxy-3-(4-(3-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)propoxy)phenyl)propionicacid,2-ethoxy-3-(4-(3-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)propyl)phenyl)propionicacid,2-methoxy-3-(4-(3-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)propyl)phenyl)propionicacid,2-propoxy-3-(4-(3-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)propyl)phenyl)propionicacid,2-benzyloxy-3-(4-(3-(4-oxa-1,7-dithia-8-aza-s-indacen-8-yl)propyl)phenyl)propionicacid; or a pharmaceutically acceptable salt thereof.
 35. The compoundaccording to claim 1 which is:3-{4-[2-(8,9-Dihydro-3,5-dithia4-aza-cyclopenta[f]azulen-4-yl)ethoxy]-phenyl}-2-ethoxy-propionicacid; or a pharmaceutically acceptable salt thereof.
 36. Apharmaceutical composition comprising, as an active ingredient, acompound according to any one of the preceding compound claims or apharmaceutically acceptable salt thereof together with apharmaceutically acceptable carrier or diluent.
 37. A compositionaccording to claim 36 in unit dosage form, comprising from about 0.05 toabout 100 mg, preferably from about 0.1 to about 50 mg of the compoundaccording to anyone of the preceding compound claims or apharmaceutically acceptable salt thereof.
 38. A pharmaceuticalcomposition useful in the treatment and/or prevention of conditionsmediated by nuclear receptors, in particular the PeroxisomeProliferator-Activated Receptors (PPAR), the composition comprising, asan active ingredient, a compound according to anyone of the precedingcompound claims or a pharmaceutically acceptable salt thereof togetherwith a pharmaceutically acceptable carrier or diluent.
 39. Apharmaceutical composition useful in the treatment and/or prevention ofdiabetes and/or obesity, the composition comprising, as an activeingredient, a compound according to anyone of the preceding compoundclaims or a pharmaceutically acceptable salt thereof together with apharmaceutically acceptable carrier or diluent.
 40. A pharmaceuticalcomposition for diabetes and/or obesity, the composition comprising, asan active ingredient, a compound according to anyone of the precedingcompound claims or a pharmaceutically acceptable salt thereof togetherwith a pharmaceutically acceptable carrier or diluent.
 41. Apharmaceutical composition according to any one of the claims 36-40 fororal, nasal, transdermal, pulmonal, or parenteral administration.
 42. Amethod for the treatment of ailments, the method comprisingadministering to a subject in need thereof an effective amount of acompound according to anyone of the preceding compound claims or apharmaceutically acceptable salt thereof, or of a composition accordingto any one of the preceding composition claims.
 43. A method for thetreatment and/or prevention of conditions mediated by nuclear receptors,in particular the Peroxisome Proliferator-Activated Receptors (PPAR),the method comprising administering to a subject in need thereof aneffective amount of a compound according to any one of the precedingcompound claims or a pharmaceutically acceptable salt thereof, or of acomposition according to anyone of the preceding claims 36-41.
 44. Amethod for the treatment and/or prevention of diabetes and/or obesity,the method comprising administering to a subject in need thereof aneffective amount of a compound according to anyone of the precedingcompound claims or a pharmaceutically acceptable salt thereof, or of acomposition according to anyone of the preceding claims 36-41.
 45. Themethod according to claims 42-44, wherein the effective amount of thecompound according to anyone of the preceding compound claims or apharmaceutically acceptable salt or ester thereof is in the range offrom about 0.05 to about 100 mg per day, preferably from about 0.1 toabout 50 mg per day.
 46. Use of a compound according to anyone of thepreceding compound claims or a pharmaceutically acceptable salt thereoffor the preparation of a medicament.
 47. Use of a compound according toanyone of the preceding compound claims or a pharmaceutically acceptablesalt thereof for the preparation of a medicament useful in the treatmentand/or prevention of conditions mediated by nuclear receptors, inparticular the Peroxisome Proliferator-Activated Receptors (PPAR). 48.Use of a compound according to anyone of the preceding compound claimsor a pharmaceutically acceptable-salt thereof for the preparation of amedicament for treatment and/or prevention of diabetes and/or obesity.49. Use of a compound according to anyone of the preceding compoundclaims or a pharmaceutically acceptable salt thereof for the preparationof a medicament for treatment and/or prevention of diabetes and obesity.